2022
150.
Rubio, Teresa; Chernigovskaya, Maria; Marquez, Susanna; Marti, Cristina; Izquierdo-Altarejos, Paula; Urios, Amparo; Montoliu, Carmina; Felipo, Vicente; Conesa, Ana; Greiff, Victor; Tarazona, Sonia
A Nextflow pipeline for T-cell receptor repertoire reconstruction and analysis from RNA sequencing data Journal Article
In: ImmunoInformatics, vol. 6, pp. 100012, 2022.
@article{Rubio2022-sg,
title = {A Nextflow pipeline for T-cell receptor repertoire reconstruction and analysis from RNA sequencing data},
author = {Teresa Rubio and Maria Chernigovskaya and Susanna Marquez and Cristina Marti and Paula Izquierdo-Altarejos and Amparo Urios and Carmina Montoliu and Vicente Felipo and Ana Conesa and Victor Greiff and Sonia Tarazona},
url = {https://www.immunoinformaticsjournal.com/action/showPdf?pii=S2667-1190%2822%2900004-0},
doi = {10.1016/j.immuno.2022.100012},
year = {2022},
date = {2022-06-01},
urldate = {2022-06-01},
journal = {ImmunoInformatics},
volume = {6},
pages = {100012},
publisher = {Elsevier},
abstract = {T-cell receptor (TCR) analysis is relevant for the study of immune system diseases. The expression of TCRs is usually measured with targeted sequencing approaches where TCR genes are selectively amplified. However, many non-targeted RNA-seq experiments also contain reads of TCR genes, which could be leveraged for TCR expression analysis while reducing sample requirements and costs. Moreover, a step-by-step pipeline for the processing of transcriptome RNA-seq reads to deliver immune repertoire data is missing, and these types of analyses are usually not included in RNA-seq studies of immunological conditions. This represents a missed opportunity for complementing them with the analysis of the immune repertoire.
We present a Nextflow pipeline for T-cell receptor repertoire reconstruction and analysis from RNA sequencing data. We used a case study where TCR repertoire profiles were recovered from bulk RNA-seq of isolated CD4 T cells from control patients, cirrhotic patients without and with Minimal Hepatic Encephalopathy (MHE). MHE is a neuropsychiatric syndrome, mediated by peripheral inflammation, that may affect cirrhotic patients. After the recovery of 498-1,114 distinct TCR beta chains per patient, repertoire analysis of patients resulted in few public clones, high diversity and elevated within-repertoire sequence similarity, independently of immune status. Additionally, TCRs associated with celiac disease and inflammatory bowel disease were significantly overrepresented in MHE patient repertoires. The provided computational pipeline functions as a resource to facilitate TCR profiling from RNA-seq data boosting immunophenotype analyses of immunological diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
T-cell receptor (TCR) analysis is relevant for the study of immune system diseases. The expression of TCRs is usually measured with targeted sequencing approaches where TCR genes are selectively amplified. However, many non-targeted RNA-seq experiments also contain reads of TCR genes, which could be leveraged for TCR expression analysis while reducing sample requirements and costs. Moreover, a step-by-step pipeline for the processing of transcriptome RNA-seq reads to deliver immune repertoire data is missing, and these types of analyses are usually not included in RNA-seq studies of immunological conditions. This represents a missed opportunity for complementing them with the analysis of the immune repertoire.
We present a Nextflow pipeline for T-cell receptor repertoire reconstruction and analysis from RNA sequencing data. We used a case study where TCR repertoire profiles were recovered from bulk RNA-seq of isolated CD4 T cells from control patients, cirrhotic patients without and with Minimal Hepatic Encephalopathy (MHE). MHE is a neuropsychiatric syndrome, mediated by peripheral inflammation, that may affect cirrhotic patients. After the recovery of 498-1,114 distinct TCR beta chains per patient, repertoire analysis of patients resulted in few public clones, high diversity and elevated within-repertoire sequence similarity, independently of immune status. Additionally, TCRs associated with celiac disease and inflammatory bowel disease were significantly overrepresented in MHE patient repertoires. The provided computational pipeline functions as a resource to facilitate TCR profiling from RNA-seq data boosting immunophenotype analyses of immunological diseases.
We present a Nextflow pipeline for T-cell receptor repertoire reconstruction and analysis from RNA sequencing data. We used a case study where TCR repertoire profiles were recovered from bulk RNA-seq of isolated CD4 T cells from control patients, cirrhotic patients without and with Minimal Hepatic Encephalopathy (MHE). MHE is a neuropsychiatric syndrome, mediated by peripheral inflammation, that may affect cirrhotic patients. After the recovery of 498-1,114 distinct TCR beta chains per patient, repertoire analysis of patients resulted in few public clones, high diversity and elevated within-repertoire sequence similarity, independently of immune status. Additionally, TCRs associated with celiac disease and inflammatory bowel disease were significantly overrepresented in MHE patient repertoires. The provided computational pipeline functions as a resource to facilitate TCR profiling from RNA-seq data boosting immunophenotype analyses of immunological diseases.
149.
Nanni, Adalena V; Morse, Alison M; Newman, Jeremy R B; Choquette, Nicole E; Wedow, Jessica M; Liu, Zihao; Leakey, Andrew D B; Conesa, Ana; Ainsworth, Elizabeth A; McIntyre, Lauren M
Variation in leaf transcriptome responses to elevated ozone corresponds with physiological sensitivity to ozone across maize inbred lines Journal Article
In: Genetics, 2022, ISSN: 1943-2631.
@article{pmid35579358,
title = {Variation in leaf transcriptome responses to elevated ozone corresponds with physiological sensitivity to ozone across maize inbred lines},
author = {Adalena V Nanni and Alison M Morse and Jeremy R B Newman and Nicole E Choquette and Jessica M Wedow and Zihao Liu and Andrew D B Leakey and Ana Conesa and Elizabeth A Ainsworth and Lauren M McIntyre},
doi = {10.1093/genetics/iyac080},
issn = {1943-2631},
year = {2022},
date = {2022-05-01},
journal = {Genetics},
abstract = {We examine the impact of sustained elevated ozone concentration on the leaf transcriptome of 5 diverse maize inbred genotypes, which vary in physiological sensitivity to ozone (B73, Mo17, Hp301, C123, NC338), using long reads to assemble transcripts and short reads to quantify expression of these transcripts. More than 99% of the long reads, 99% of the assembled transcripts, and 97% of the short reads map to both B73 and Mo17 reference genomes. Approximately 95% of the genes with assembled transcripts belong to known B73-Mo17 syntenic loci and 94% of genes with assembled transcripts are present in all temperate lines in the NAM pan-genome. While there is limited evidence for alternative splicing in response to ozone stress, there is a difference in the magnitude of differential expression among the 5 genotypes. The transcriptional response to sustained ozone stress in the ozone resistant B73 genotype (151 genes) was modest, while more than 3,300 genes were significantly differentially expressed in the more sensitive NC338 genotype. There is the potential for tandem duplication in 30% of genes with assembled transcripts, but there is no obvious association between potential tandem duplication and differential expression. Genes with a common response across the 5 genotypes (83 genes) were associated with photosynthesis, in particular photosystem I. The functional annotation of genes not differentially expressed in B73 but responsive in the other 4 genotypes (789) identifies reactive oxygen species. This suggests that B73 has a different response to long term ozone exposure than the other 4 genotypes. The relative magnitude of the genotypic response to ozone, and the enrichment analyses are consistent regardless of whether aligning short reads to: long read assembled transcripts; the B73 reference; the Mo17 reference. We find that prolonged ozone exposure directly impacts the photosynthetic machinery of the leaf.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We examine the impact of sustained elevated ozone concentration on the leaf transcriptome of 5 diverse maize inbred genotypes, which vary in physiological sensitivity to ozone (B73, Mo17, Hp301, C123, NC338), using long reads to assemble transcripts and short reads to quantify expression of these transcripts. More than 99% of the long reads, 99% of the assembled transcripts, and 97% of the short reads map to both B73 and Mo17 reference genomes. Approximately 95% of the genes with assembled transcripts belong to known B73-Mo17 syntenic loci and 94% of genes with assembled transcripts are present in all temperate lines in the NAM pan-genome. While there is limited evidence for alternative splicing in response to ozone stress, there is a difference in the magnitude of differential expression among the 5 genotypes. The transcriptional response to sustained ozone stress in the ozone resistant B73 genotype (151 genes) was modest, while more than 3,300 genes were significantly differentially expressed in the more sensitive NC338 genotype. There is the potential for tandem duplication in 30% of genes with assembled transcripts, but there is no obvious association between potential tandem duplication and differential expression. Genes with a common response across the 5 genotypes (83 genes) were associated with photosynthesis, in particular photosystem I. The functional annotation of genes not differentially expressed in B73 but responsive in the other 4 genotypes (789) identifies reactive oxygen species. This suggests that B73 has a different response to long term ozone exposure than the other 4 genotypes. The relative magnitude of the genotypic response to ozone, and the enrichment analyses are consistent regardless of whether aligning short reads to: long read assembled transcripts; the B73 reference; the Mo17 reference. We find that prolonged ozone exposure directly impacts the photosynthetic machinery of the leaf.
148.
Liu, Tianyuan; Salguero, Pedro; Petek, Marko; Martinez-Mira, Carlos; Balzano-Nogueira, Leandro; Ramšak, Živa; McIntyre, Lauren; Gruden, Kristina; Tarazona, Sonia; Conesa, Ana
PaintOmics 4: new tools for the integrative analysis of multi-omics datasets supported by multiple pathway databases Journal Article
In: Nucleic Acids Res, 2022, ISSN: 1362-4962.
@article{pmid35609982,
title = {PaintOmics 4: new tools for the integrative analysis of multi-omics datasets supported by multiple pathway databases},
author = {Tianyuan Liu and Pedro Salguero and Marko Petek and Carlos Martinez-Mira and Leandro Balzano-Nogueira and Živa Ramšak and Lauren McIntyre and Kristina Gruden and Sonia Tarazona and Ana Conesa},
doi = {10.1093/nar/gkac352},
issn = {1362-4962},
year = {2022},
date = {2022-05-01},
journal = {Nucleic Acids Res},
abstract = {PaintOmics is a web server for the integrative analysis and visualisation of multi-omics datasets using biological pathway maps. PaintOmics 4 has several notable updates that improve and extend analyses. Three pathway databases are now supported: KEGG, Reactome and MapMan, providing more comprehensive pathway knowledge for animals and plants. New metabolite analysis methods fill gaps in traditional pathway-based enrichment methods. The metabolite hub analysis selects compounds with a high number of significant genes in their neighbouring network, suggesting regulation by gene expression changes. The metabolite class activity analysis tests the hypothesis that a metabolic class has a higher-than-expected proportion of significant elements, indicating that these compounds are regulated in the experiment. Finally, PaintOmics 4 includes a regulatory omics module to analyse the contribution of trans-regulatory layers (microRNA and transcription factors, RNA-binding proteins) to regulate pathways. We show the performance of PaintOmics 4 on both mouse and plant data to highlight how these new analysis features provide novel insights into regulatory biology. PaintOmics 4 is available at https://paintomics.org/.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PaintOmics is a web server for the integrative analysis and visualisation of multi-omics datasets using biological pathway maps. PaintOmics 4 has several notable updates that improve and extend analyses. Three pathway databases are now supported: KEGG, Reactome and MapMan, providing more comprehensive pathway knowledge for animals and plants. New metabolite analysis methods fill gaps in traditional pathway-based enrichment methods. The metabolite hub analysis selects compounds with a high number of significant genes in their neighbouring network, suggesting regulation by gene expression changes. The metabolite class activity analysis tests the hypothesis that a metabolic class has a higher-than-expected proportion of significant elements, indicating that these compounds are regulated in the experiment. Finally, PaintOmics 4 includes a regulatory omics module to analyse the contribution of trans-regulatory layers (microRNA and transcription factors, RNA-binding proteins) to regulate pathways. We show the performance of PaintOmics 4 on both mouse and plant data to highlight how these new analysis features provide novel insights into regulatory biology. PaintOmics 4 is available at https://paintomics.org/.
147.
Ugidos, Manuel; Nueda, María José; Prats-Montalbán, José M; Ferrer, Alberto; Conesa, Ana; Tarazona, Sonia
MultiBaC: An R package to remove batch effects in multi-omic experiments Journal Article
In: Bioinformatics, 2022.
@article{Ugidos2022-sk,
title = {MultiBaC: An R package to remove batch effects in multi-omic experiments},
author = {Manuel Ugidos and María José Nueda and José M Prats-Montalbán and Alberto Ferrer and Ana Conesa and Sonia Tarazona},
url = {https://watermark.silverchair.com/btac132.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAzEwggMtBgkqhkiG9w0BBwagggMeMIIDGgIBADCCAxMGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMeEcUTCRMnmsoFyy8AgEQgIIC5JWHJW_tG0ZfXPRWz1anVh55AhxVg26g2g9wdqQAgT7LBtdVIlHfR_v5GbzIud725UlWMpSwL-oFFwiYCDSoGweumU1IH6_XhfgfUfI-AFBEuQDXTRYjtTpSoH1VlIXMsXd1OtVdfE6aj8zG1iNSSirVljWzpRdJfZolvD1GoqXOySVndzFgV4FEC2eHxbvABFV8bVpqO9T6QWxgwy_5qY1faQ9XUsywBxq3SbGV1uKhqrcSEOePoLYUIXCRLnYaIXfsbZIKxHd4JWHYSUPzHfgH-tSUTkCZjqfv0PI1DNj9vXhsHL0eMSEdtSc2Kdh1h06r7Y0ShpDcDzv1d77wtlX00r6npnlnVwv8XKJURx8kY_vkVOJO5XFPqyl4JQm4Nd6r0kvuBPJ9p0JUTpz5kJOxrtfcS96Ql5YPC8p-5qccBtVbWzaApqdubHm1o7D7z9X3rKA3053pPoQ8HuEsPqe7Keuoqvo1gpYbJICPDm7-raQj7YIwFS9iZBCAphwsp4MXpOhEKA23vBdpv4b_pMANVBHHq33WVFJjBneTeJliYFv_Ynk6W1KrbgTqel8f0mF9knfrOhftEB-Eod3uj0nrCkmB31jwlGC0A6jaF_mJ06WY7hekKmrAki07356jI2cc5VGyGGfD8uRvuBV2wPxXTlkZfq9vwLZbX9qNuhSg14aTUXvW89nbF4uNI3h8dowM7bvUV6Qdf2eabAoBg7cYervp5twQLlMHfSmcwMnvB4Oit4w9UD3xaed-osA1o6jYVCofUN0Qcq9oeeutC9NxYpmziEcVXu4Uz5aIgpakIaHcUvYHtySGrk85Pu9-CmrY-Ek6M3OXJHV7drvq_8dfKKrlj-5xDoulwdRjCwOYkLr88o-r38-QfEsanwmjEqFjZH93e0Rm3wNZVn1j1NRGLrdzclEldx_DXTd3vuh6jxv-CrtRxQ9pK-n73Kq4msmTKiHV6Ubg-qcYREbMZ1e4NpKp},
doi = {10.1093/bioinformatics/btac132},
year = {2022},
date = {2022-03-01},
urldate = {2022-03-01},
journal = {Bioinformatics},
publisher = {Öxford University Press (OUP)},
abstract = {MOTIVATION: Batch effects in omics datasets are usually a source
of technical noise that masks the biological signal and hampers
data analysis. Batch effect removal has been widely addressed
for individual omics technologies. However, multi-omic datasets
may combine data obtained in different batches where omics type
and batch are often confounded. Moreover, systematic biases may
be introduced without notice during data acquisition, which
creates a hidden batch effect. Current methods fail to address
batch effect correction in these cases. RESULTS: In this paper
we introduce the MultiBaC R package, a tool for batch effect
removal in multi-omics and hidden batch effect scenarios. The
package includes a diversity of graphical outputs for model
validation and assessment of the batch effect correction.
AVAILABILITY: MultiBaC package is available on Bioconductor
(https://www.bioconductor.org/packages/release/bioc/html/MultiBaC.html)
and GitHub (https://github.com/ConesaLab/MultiBaC.git).
SUPPLEMENTARY INFORMATION: Supplementary data are available at
Bioinformatics online.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
MOTIVATION: Batch effects in omics datasets are usually a source
of technical noise that masks the biological signal and hampers
data analysis. Batch effect removal has been widely addressed
for individual omics technologies. However, multi-omic datasets
may combine data obtained in different batches where omics type
and batch are often confounded. Moreover, systematic biases may
be introduced without notice during data acquisition, which
creates a hidden batch effect. Current methods fail to address
batch effect correction in these cases. RESULTS: In this paper
we introduce the MultiBaC R package, a tool for batch effect
removal in multi-omics and hidden batch effect scenarios. The
package includes a diversity of graphical outputs for model
validation and assessment of the batch effect correction.
AVAILABILITY: MultiBaC package is available on Bioconductor
(https://www.bioconductor.org/packages/release/bioc/html/MultiBaC.html)
and GitHub (https://github.com/ConesaLab/MultiBaC.git).
SUPPLEMENTARY INFORMATION: Supplementary data are available at
Bioinformatics online.
of technical noise that masks the biological signal and hampers
data analysis. Batch effect removal has been widely addressed
for individual omics technologies. However, multi-omic datasets
may combine data obtained in different batches where omics type
and batch are often confounded. Moreover, systematic biases may
be introduced without notice during data acquisition, which
creates a hidden batch effect. Current methods fail to address
batch effect correction in these cases. RESULTS: In this paper
we introduce the MultiBaC R package, a tool for batch effect
removal in multi-omics and hidden batch effect scenarios. The
package includes a diversity of graphical outputs for model
validation and assessment of the batch effect correction.
AVAILABILITY: MultiBaC package is available on Bioconductor
(https://www.bioconductor.org/packages/release/bioc/html/MultiBaC.html)
and GitHub (https://github.com/ConesaLab/MultiBaC.git).
SUPPLEMENTARY INFORMATION: Supplementary data are available at
Bioinformatics online.
146.
Miller, Rachel M; Jordan, Ben T; Mehlferber, Madison M; Jeffery, Erin D; Chatzipantsiou, Christina; Kaur, Simi; Millikin, Robert J; Dai, Yunxiang; Tiberi, Simone; Castaldi, Peter J; Shortreed, Michael R; Luckey, Chance John; Conesa, Ana; Smith, Lloyd M; Mays, Anne Deslattes; Sheynkman, Gloria M
Enhanced protein isoform characterization through long-read proteogenomics Journal Article
In: Genome Biol., vol. 23, no. 1, pp. 69, 2022.
@article{Miller2022-sz,
title = {Enhanced protein isoform characterization through long-read proteogenomics},
author = {Rachel M Miller and Ben T Jordan and Madison M Mehlferber and Erin D Jeffery and Christina Chatzipantsiou and Simi Kaur and Robert J Millikin and Yunxiang Dai and Simone Tiberi and Peter J Castaldi and Michael R Shortreed and Chance John Luckey and Ana Conesa and Lloyd M Smith and Anne Deslattes Mays and Gloria M Sheynkman},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892804/pdf/13059_2022_Article_2624.pdf},
doi = {10.1186/s13059-022-02624-y},
year = {2022},
date = {2022-03-01},
urldate = {2022-03-01},
journal = {Genome Biol.},
volume = {23},
number = {1},
pages = {69},
publisher = {Springer Science and Business Media LLC},
abstract = {BACKGROUND: The detection of physiologically relevant protein
isoforms encoded by the human genome is critical to biomedicine.
Mass spectrometry (MS)-based proteomics is the preeminent method
for protein detection, but isoform-resolved proteomic analysis
relies on accurate reference databases that match the sample;
neither a subset nor a superset database is ideal. Long-read RNA
sequencing (e.g., PacBio or Oxford Nanopore) provides
full-length transcripts which can be used to predict full-length
protein isoforms. RESULTS: We describe here a long-read
proteogenomics approach for integrating sample-matched long-read
RNA-seq and MS-based proteomics data to enhance isoform
characterization. We introduce a classification scheme for
protein isoforms, discover novel protein isoforms, and present
the first protein inference algorithm for the direct
incorporation of long-read transcriptome data to enable
detection of protein isoforms previously intractable to MS-based
detection. We have released an open-source Nextflow pipeline
that integrates long-read sequencing in a proteomic workflow for
isoform-resolved analysis. CONCLUSIONS: Our work suggests that
the incorporation of long-read sequencing and proteomic data can
facilitate improved characterization of human protein isoform
diversity. Our first-generation pipeline provides a strong
foundation for future development of long-read proteogenomics
and its adoption for both basic and translational research.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The detection of physiologically relevant protein
isoforms encoded by the human genome is critical to biomedicine.
Mass spectrometry (MS)-based proteomics is the preeminent method
for protein detection, but isoform-resolved proteomic analysis
relies on accurate reference databases that match the sample;
neither a subset nor a superset database is ideal. Long-read RNA
sequencing (e.g., PacBio or Oxford Nanopore) provides
full-length transcripts which can be used to predict full-length
protein isoforms. RESULTS: We describe here a long-read
proteogenomics approach for integrating sample-matched long-read
RNA-seq and MS-based proteomics data to enhance isoform
characterization. We introduce a classification scheme for
protein isoforms, discover novel protein isoforms, and present
the first protein inference algorithm for the direct
incorporation of long-read transcriptome data to enable
detection of protein isoforms previously intractable to MS-based
detection. We have released an open-source Nextflow pipeline
that integrates long-read sequencing in a proteomic workflow for
isoform-resolved analysis. CONCLUSIONS: Our work suggests that
the incorporation of long-read sequencing and proteomic data can
facilitate improved characterization of human protein isoform
diversity. Our first-generation pipeline provides a strong
foundation for future development of long-read proteogenomics
and its adoption for both basic and translational research.
isoforms encoded by the human genome is critical to biomedicine.
Mass spectrometry (MS)-based proteomics is the preeminent method
for protein detection, but isoform-resolved proteomic analysis
relies on accurate reference databases that match the sample;
neither a subset nor a superset database is ideal. Long-read RNA
sequencing (e.g., PacBio or Oxford Nanopore) provides
full-length transcripts which can be used to predict full-length
protein isoforms. RESULTS: We describe here a long-read
proteogenomics approach for integrating sample-matched long-read
RNA-seq and MS-based proteomics data to enhance isoform
characterization. We introduce a classification scheme for
protein isoforms, discover novel protein isoforms, and present
the first protein inference algorithm for the direct
incorporation of long-read transcriptome data to enable
detection of protein isoforms previously intractable to MS-based
detection. We have released an open-source Nextflow pipeline
that integrates long-read sequencing in a proteomic workflow for
isoform-resolved analysis. CONCLUSIONS: Our work suggests that
the incorporation of long-read sequencing and proteomic data can
facilitate improved characterization of human protein isoform
diversity. Our first-generation pipeline provides a strong
foundation for future development of long-read proteogenomics
and its adoption for both basic and translational research.
145.
McIntyre, Lauren M; Huertas, Francisco; Morse, Alison M; Kaletsky, Rachel; Murphy, Coleen T; Kalia, Vrinda; Miller, Gary W; Moskalenko, Olexander; Conesa, Ana; Mor, Danielle E
GAIT-GM integrative cross-omics analyses reveal cholinergic defects in a C. elegans model of Parkinson's disease Journal Article
In: Sci. Rep., vol. 12, no. 1, pp. 3268, 2022.
@article{McIntyre2022-xu,
title = {GAIT-GM integrative cross-omics analyses reveal cholinergic defects in a C. elegans model of Parkinson's disease},
author = {Lauren M McIntyre and Francisco Huertas and Alison M Morse and Rachel Kaletsky and Coleen T Murphy and Vrinda Kalia and Gary W Miller and Olexander Moskalenko and Ana Conesa and Danielle E Mor},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885929/pdf/41598_2022_Article_7238.pdf},
doi = {10.1038/s41598-022-07238-9},
year = {2022},
date = {2022-02-01},
urldate = {2022-02-01},
journal = {Sci. Rep.},
volume = {12},
number = {1},
pages = {3268},
publisher = {Springer Science and Business Media LLC},
abstract = {Parkinson's disease (PD) is a disabling neurodegenerative
disorder in which multiple cell types, including dopaminergic
and cholinergic neurons, are affected. The mechanisms of
neurodegeneration in PD are not fully understood, limiting the
development of therapies directed at disease-relevant molecular
targets. C. elegans is a genetically tractable model system that
can be used to disentangle disease mechanisms in complex
diseases such as PD. Such mechanisms can be studied combining
high-throughput molecular profiling technologies such as
transcriptomics and metabolomics. However, the integrative
analysis of multi-omics data in order to unravel disease
mechanisms is a challenging task without advanced bioinformatics
training. Galaxy, a widely-used resource for enabling
bioinformatics analysis by the broad scientific community, has
poor representation of multi-omics integration pipelines. We
present the integrative analysis of gene expression and
metabolite levels of a C. elegans PD model using GAIT-GM, a new
Galaxy tool for multi-omics data analysis. Using GAIT-GM, we
discovered an association between branched-chain amino acid
metabolism and cholinergic neurons in the C. elegans PD model.
An independent follow-up experiment uncovered cholinergic
neurodegeneration in the C. elegans model that is consistent
with cholinergic cell loss observed in PD. GAIT-GM is an easy to
use Galaxy-based tool for generating novel testable hypotheses
of disease mechanisms involving gene-metabolite relationships.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Parkinson's disease (PD) is a disabling neurodegenerative
disorder in which multiple cell types, including dopaminergic
and cholinergic neurons, are affected. The mechanisms of
neurodegeneration in PD are not fully understood, limiting the
development of therapies directed at disease-relevant molecular
targets. C. elegans is a genetically tractable model system that
can be used to disentangle disease mechanisms in complex
diseases such as PD. Such mechanisms can be studied combining
high-throughput molecular profiling technologies such as
transcriptomics and metabolomics. However, the integrative
analysis of multi-omics data in order to unravel disease
mechanisms is a challenging task without advanced bioinformatics
training. Galaxy, a widely-used resource for enabling
bioinformatics analysis by the broad scientific community, has
poor representation of multi-omics integration pipelines. We
present the integrative analysis of gene expression and
metabolite levels of a C. elegans PD model using GAIT-GM, a new
Galaxy tool for multi-omics data analysis. Using GAIT-GM, we
discovered an association between branched-chain amino acid
metabolism and cholinergic neurons in the C. elegans PD model.
An independent follow-up experiment uncovered cholinergic
neurodegeneration in the C. elegans model that is consistent
with cholinergic cell loss observed in PD. GAIT-GM is an easy to
use Galaxy-based tool for generating novel testable hypotheses
of disease mechanisms involving gene-metabolite relationships.
disorder in which multiple cell types, including dopaminergic
and cholinergic neurons, are affected. The mechanisms of
neurodegeneration in PD are not fully understood, limiting the
development of therapies directed at disease-relevant molecular
targets. C. elegans is a genetically tractable model system that
can be used to disentangle disease mechanisms in complex
diseases such as PD. Such mechanisms can be studied combining
high-throughput molecular profiling technologies such as
transcriptomics and metabolomics. However, the integrative
analysis of multi-omics data in order to unravel disease
mechanisms is a challenging task without advanced bioinformatics
training. Galaxy, a widely-used resource for enabling
bioinformatics analysis by the broad scientific community, has
poor representation of multi-omics integration pipelines. We
present the integrative analysis of gene expression and
metabolite levels of a C. elegans PD model using GAIT-GM, a new
Galaxy tool for multi-omics data analysis. Using GAIT-GM, we
discovered an association between branched-chain amino acid
metabolism and cholinergic neurons in the C. elegans PD model.
An independent follow-up experiment uncovered cholinergic
neurodegeneration in the C. elegans model that is consistent
with cholinergic cell loss observed in PD. GAIT-GM is an easy to
use Galaxy-based tool for generating novel testable hypotheses
of disease mechanisms involving gene-metabolite relationships.
144.
Beltrame, Anna; Salguero, Pedro; Rossi, Emanuela; Conesa, Ana; Moro, Lucia; Bettini, Laura Rachele; Rizzi, Eleonora; DÁngió, Mariella; Deiana, Michela; Piubelli, Chiara; Rebora, Paola; Duranti, Silvia; Bonfanti, Paolo; Capua, Ilaria; Tarazona, Sonia; Valsecchi, Maria Grazia
In: Front. Immunol., vol. 13, pp. 834851, 2022.
@article{Beltrame2022-bt,
title = {Association between sex hormone levels and clinical outcomes in patients with COVID-19 admitted to hospital: An observational, retrospective, cohort study},
author = {Anna Beltrame and Pedro Salguero and Emanuela Rossi and Ana Conesa and Lucia Moro and Laura Rachele Bettini and Eleonora Rizzi and Mariella DÁngió and Michela Deiana and Chiara Piubelli and Paola Rebora and Silvia Duranti and Paolo Bonfanti and Ilaria Capua and Sonia Tarazona and Maria Grazia Valsecchi},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829540/pdf/fimmu-13-834851.pdf},
doi = {10.3389/fimmu.2022.834851},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Front. Immunol.},
volume = {13},
pages = {834851},
abstract = {Understanding the cause of sex disparities in COVID-19 outcomes
is a major challenge. We investigate sex hormone levels and their
association with outcomes in COVID-19 patients, stratified by sex
and age. This observational, retrospective, cohort study included
138 patients aged 18 years or older with COVID-19, hospitalized
in Italy between February 1 and May 30, 2020. The association
between sex hormones (testosterone, estradiol, progesterone,
dehydroepiandrosterone) and outcomes (ARDS, severe COVID-19,
in-hospital mortality) was explored in 120 patients aged 50 years
and over. STROBE checklist was followed. The median age was 73.5
years [IQR 61, 82]; 55.8% were male. In older males,
testosterone was lower if ARDS and severe COVID-19 were reported than if not (3.6 vs. 5.3 nmol/L},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Understanding the cause of sex disparities in COVID-19 outcomes
is a major challenge. We investigate sex hormone levels and their
association with outcomes in COVID-19 patients, stratified by sex
and age. This observational, retrospective, cohort study included
138 patients aged 18 years or older with COVID-19, hospitalized
in Italy between February 1 and May 30, 2020. The association
between sex hormones (testosterone, estradiol, progesterone,
dehydroepiandrosterone) and outcomes (ARDS, severe COVID-19,
in-hospital mortality) was explored in 120 patients aged 50 years
and over. STROBE checklist was followed. The median age was 73.5
years [IQR 61, 82]; 55.8% were male. In older males,
testosterone was lower if ARDS and severe COVID-19 were reported than if not (3.6 vs. 5.3 nmol/L
is a major challenge. We investigate sex hormone levels and their
association with outcomes in COVID-19 patients, stratified by sex
and age. This observational, retrospective, cohort study included
138 patients aged 18 years or older with COVID-19, hospitalized
in Italy between February 1 and May 30, 2020. The association
between sex hormones (testosterone, estradiol, progesterone,
dehydroepiandrosterone) and outcomes (ARDS, severe COVID-19,
in-hospital mortality) was explored in 120 patients aged 50 years
and over. STROBE checklist was followed. The median age was 73.5
years [IQR 61, 82]; 55.8% were male. In older males,
testosterone was lower if ARDS and severe COVID-19 were reported than if not (3.6 vs. 5.3 nmol/L
143.
Zhang, Runxuan; Kuo, Richard; Coulter, Max; Calixto, Cristiane P G; Entizne, Juan Carlos; Guo, Wenbin; Marquez, Yamile; Milne, Linda; Riegler, Stefan; Matsui, Akihiro; Tanaka, Maho; Harvey, Sarah; Gao, Yubang; Wießner-Kroh, Theresa; Paniagua, Alejandro; Crespi, Martin; Denby, Katherine; Hur, Asa Ben; Huq, Enamul; Jantsch, Michael; Jarmolowski, Artur; Koester, Tino; Laubinger, Sascha; Li, Qingshun Quinn; Gu, Lianfeng; Seki, Motoaki; Staiger, Dorothee; Sunkar, Ramanjulu; Szweykowska-Kulinska, Zofia; Tu, Shih-Long; Wachter, Andreas; Waugh, Robbie; Xiong, Liming; Zhang, Xiao-Ning; Conesa, Ana; Reddy, Anireddy S N; Barta, Andrea; Kalyna, Maria; Brown, John W S
A high-resolution single-molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis Journal Article
In: Genome Biol, vol. 23, no. 1, pp. 149, 2022, ISSN: 1474-760X.
@article{pmid35799267,
title = {A high-resolution single-molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis},
author = {Runxuan Zhang and Richard Kuo and Max Coulter and Cristiane P G Calixto and Juan Carlos Entizne and Wenbin Guo and Yamile Marquez and Linda Milne and Stefan Riegler and Akihiro Matsui and Maho Tanaka and Sarah Harvey and Yubang Gao and Theresa Wießner-Kroh and Alejandro Paniagua and Martin Crespi and Katherine Denby and Asa Ben Hur and Enamul Huq and Michael Jantsch and Artur Jarmolowski and Tino Koester and Sascha Laubinger and Qingshun Quinn Li and Lianfeng Gu and Motoaki Seki and Dorothee Staiger and Ramanjulu Sunkar and Zofia Szweykowska-Kulinska and Shih-Long Tu and Andreas Wachter and Robbie Waugh and Liming Xiong and Xiao-Ning Zhang and Ana Conesa and Anireddy S N Reddy and Andrea Barta and Maria Kalyna and John W S Brown},
doi = {10.1186/s13059-022-02711-0},
issn = {1474-760X},
year = {2022},
date = {2022-01-01},
journal = {Genome Biol},
volume = {23},
number = {1},
pages = {149},
abstract = {BACKGROUND: Accurate and comprehensive annotation of transcript sequences is essential for transcript quantification and differential gene and transcript expression analysis. Single-molecule long-read sequencing technologies provide improved integrity of transcript structures including alternative splicing, and transcription start and polyadenylation sites. However, accuracy is significantly affected by sequencing errors, mRNA degradation, or incomplete cDNA synthesis.
RESULTS: We present a new and comprehensive Arabidopsis thaliana Reference Transcript Dataset 3 (AtRTD3). AtRTD3 contains over 169,000 transcripts-twice that of the best current Arabidopsis transcriptome and including over 1500 novel genes. Seventy-eight percent of transcripts are from Iso-seq with accurately defined splice junctions and transcription start and end sites. We develop novel methods to determine splice junctions and transcription start and end sites accurately. Mismatch profiles around splice junctions provide a powerful feature to distinguish correct splice junctions and remove false splice junctions. Stratified approaches identify high-confidence transcription start and end sites and remove fragmentary transcripts due to degradation. AtRTD3 is a major improvement over existing transcriptomes as demonstrated by analysis of an Arabidopsis cold response RNA-seq time-series. AtRTD3 provides higher resolution of transcript expression profiling and identifies cold-induced differential transcription start and polyadenylation site usage.
CONCLUSIONS: AtRTD3 is the most comprehensive Arabidopsis transcriptome currently. It improves the precision of differential gene and transcript expression, differential alternative splicing, and transcription start/end site usage analysis from RNA-seq data. The novel methods for identifying accurate splice junctions and transcription start/end sites are widely applicable and will improve single-molecule sequencing analysis from any species.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Accurate and comprehensive annotation of transcript sequences is essential for transcript quantification and differential gene and transcript expression analysis. Single-molecule long-read sequencing technologies provide improved integrity of transcript structures including alternative splicing, and transcription start and polyadenylation sites. However, accuracy is significantly affected by sequencing errors, mRNA degradation, or incomplete cDNA synthesis.
RESULTS: We present a new and comprehensive Arabidopsis thaliana Reference Transcript Dataset 3 (AtRTD3). AtRTD3 contains over 169,000 transcripts-twice that of the best current Arabidopsis transcriptome and including over 1500 novel genes. Seventy-eight percent of transcripts are from Iso-seq with accurately defined splice junctions and transcription start and end sites. We develop novel methods to determine splice junctions and transcription start and end sites accurately. Mismatch profiles around splice junctions provide a powerful feature to distinguish correct splice junctions and remove false splice junctions. Stratified approaches identify high-confidence transcription start and end sites and remove fragmentary transcripts due to degradation. AtRTD3 is a major improvement over existing transcriptomes as demonstrated by analysis of an Arabidopsis cold response RNA-seq time-series. AtRTD3 provides higher resolution of transcript expression profiling and identifies cold-induced differential transcription start and polyadenylation site usage.
CONCLUSIONS: AtRTD3 is the most comprehensive Arabidopsis transcriptome currently. It improves the precision of differential gene and transcript expression, differential alternative splicing, and transcription start/end site usage analysis from RNA-seq data. The novel methods for identifying accurate splice junctions and transcription start/end sites are widely applicable and will improve single-molecule sequencing analysis from any species.
RESULTS: We present a new and comprehensive Arabidopsis thaliana Reference Transcript Dataset 3 (AtRTD3). AtRTD3 contains over 169,000 transcripts-twice that of the best current Arabidopsis transcriptome and including over 1500 novel genes. Seventy-eight percent of transcripts are from Iso-seq with accurately defined splice junctions and transcription start and end sites. We develop novel methods to determine splice junctions and transcription start and end sites accurately. Mismatch profiles around splice junctions provide a powerful feature to distinguish correct splice junctions and remove false splice junctions. Stratified approaches identify high-confidence transcription start and end sites and remove fragmentary transcripts due to degradation. AtRTD3 is a major improvement over existing transcriptomes as demonstrated by analysis of an Arabidopsis cold response RNA-seq time-series. AtRTD3 provides higher resolution of transcript expression profiling and identifies cold-induced differential transcription start and polyadenylation site usage.
CONCLUSIONS: AtRTD3 is the most comprehensive Arabidopsis transcriptome currently. It improves the precision of differential gene and transcript expression, differential alternative splicing, and transcription start/end site usage analysis from RNA-seq data. The novel methods for identifying accurate splice junctions and transcription start/end sites are widely applicable and will improve single-molecule sequencing analysis from any species.
2021
142.
Turpín-Sevilla, María Del Carmen; Pérez-Sanz, Fernando; García-Solano, José; Sebastián-León, Patricia; Trujillo-Santos, Javier; Carbonell, Pablo; Estrada, Eduardo; Tuomisto, Anne; Herruzo, Irene; Fennell, Lochlan J; Mäkinen, Markus J; Rodríguez-Braun, Edith; Whitehall, Vicki L J; Conesa, Ana; Conesa-Zamora, Pablo
In: Cancers (Basel), vol. 13, no. 20, pp. 5165, 2021.
@article{Turpin-Sevilla2021-vy,
title = {Global methylome scores correlate with histological subtypes of colorectal carcinoma and show different associations with common clinical and molecular features},
author = {María Del Carmen Turpín-Sevilla and Fernando Pérez-Sanz and José García-Solano and Patricia Sebastián-León and Javier Trujillo-Santos and Pablo Carbonell and Eduardo Estrada and Anne Tuomisto and Irene Herruzo and Lochlan J Fennell and Markus J Mäkinen and Edith Rodríguez-Braun and Vicki L J Whitehall and Ana Conesa and Pablo Conesa-Zamora},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533997/pdf/cancers-13-05165.pdf},
doi = {10.3390/cancers13205165},
year = {2021},
date = {2021-10-01},
urldate = {2021-10-01},
journal = {Cancers (Basel)},
volume = {13},
number = {20},
pages = {5165},
publisher = {MDPI AG},
abstract = {BACKGROUND: The typical methylation patterns associated with
cancer are hypermethylation at gene promoters and global genome
hypomethylation. Aberrant CpG island hypermethylation at
promoter regions and global genome hypomethylation have not been
associated with histological colorectal carcinomas (CRC)
subsets. Using Illumina's 450 k Infinium Human Methylation
beadchip, the methylome of 82 CRCs were analyzed, comprising
different histological subtypes: 40 serrated adenocarcinomas
(SAC), 32 conventional carcinomas (CC) and 10 CRCs showing
histological and molecular features of microsatellite
instability (hmMSI-H), and, additionally, 35 normal adjacent
mucosae. Scores reflecting the overall methylation at 250 bp, 1
kb and 2 kb from the transcription starting site (TSS) were
studied. RESULTS: SAC has an intermediate methylation pattern
between CC and hmMSI-H for the three genome locations. In
addition, the shift from promoter hypermethylation to genomic
hypomethylation occurs at a small sequence between 250 bp and 1
Kb from the gene TSS, and an asymmetric distribution of
methylation was observed between both sides of the CpG islands
(N vs. S shores). CONCLUSION: These findings show that different
histological subtypes of CRC have a particular global
methylation pattern depending on sequence distance to TSS and
highlight the so far underestimated importance of CpGs
aberrantly hypomethylated in the clinical phenotype of CRCs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The typical methylation patterns associated with
cancer are hypermethylation at gene promoters and global genome
hypomethylation. Aberrant CpG island hypermethylation at
promoter regions and global genome hypomethylation have not been
associated with histological colorectal carcinomas (CRC)
subsets. Using Illumina's 450 k Infinium Human Methylation
beadchip, the methylome of 82 CRCs were analyzed, comprising
different histological subtypes: 40 serrated adenocarcinomas
(SAC), 32 conventional carcinomas (CC) and 10 CRCs showing
histological and molecular features of microsatellite
instability (hmMSI-H), and, additionally, 35 normal adjacent
mucosae. Scores reflecting the overall methylation at 250 bp, 1
kb and 2 kb from the transcription starting site (TSS) were
studied. RESULTS: SAC has an intermediate methylation pattern
between CC and hmMSI-H for the three genome locations. In
addition, the shift from promoter hypermethylation to genomic
hypomethylation occurs at a small sequence between 250 bp and 1
Kb from the gene TSS, and an asymmetric distribution of
methylation was observed between both sides of the CpG islands
(N vs. S shores). CONCLUSION: These findings show that different
histological subtypes of CRC have a particular global
methylation pattern depending on sequence distance to TSS and
highlight the so far underestimated importance of CpGs
aberrantly hypomethylated in the clinical phenotype of CRCs.
cancer are hypermethylation at gene promoters and global genome
hypomethylation. Aberrant CpG island hypermethylation at
promoter regions and global genome hypomethylation have not been
associated with histological colorectal carcinomas (CRC)
subsets. Using Illumina's 450 k Infinium Human Methylation
beadchip, the methylome of 82 CRCs were analyzed, comprising
different histological subtypes: 40 serrated adenocarcinomas
(SAC), 32 conventional carcinomas (CC) and 10 CRCs showing
histological and molecular features of microsatellite
instability (hmMSI-H), and, additionally, 35 normal adjacent
mucosae. Scores reflecting the overall methylation at 250 bp, 1
kb and 2 kb from the transcription starting site (TSS) were
studied. RESULTS: SAC has an intermediate methylation pattern
between CC and hmMSI-H for the three genome locations. In
addition, the shift from promoter hypermethylation to genomic
hypomethylation occurs at a small sequence between 250 bp and 1
Kb from the gene TSS, and an asymmetric distribution of
methylation was observed between both sides of the CpG islands
(N vs. S shores). CONCLUSION: These findings show that different
histological subtypes of CRC have a particular global
methylation pattern depending on sequence distance to TSS and
highlight the so far underestimated importance of CpGs
aberrantly hypomethylated in the clinical phenotype of CRCs.
141.
Tarazona, Sonia; Arzalluz-Luque, Angeles; Conesa, Ana
Undisclosed, unmet and neglected challenges in multi-omics studies Journal Article
In: Nature Computational Science, vol. 1, no. 6, pp. 395-402, 2021, ISSN: 2662-8457.
@article{Tarazona2021,
title = {Undisclosed, unmet and neglected challenges in multi-omics studies},
author = {Sonia Tarazona and Angeles Arzalluz-Luque and Ana Conesa},
url = {http://conesalab.org/wp-content/uploads/2021/07/Undisclosed-unmet-and-neglected-challenges-in-multi-omics-studies-1.pdf},
doi = {10.1038/s43588-021-00086-z},
issn = {2662-8457},
year = {2021},
date = {2021-06-01},
journal = {Nature Computational Science},
volume = {1},
number = {6},
pages = {395-402},
abstract = {Multi-omics approaches have become a reality in both large genomics projects and small laboratories. However, the multi-omics research community still faces a number of issues that have either not been sufficiently discussed or for which current solutions are still limited. In this Perspective, we elaborate on these limitations and suggest points of attention for future research. We finally discuss new opportunities and challenges brought to the field by the rapid development of single-cell high-throughput molecular technologies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Multi-omics approaches have become a reality in both large genomics projects and small laboratories. However, the multi-omics research community still faces a number of issues that have either not been sufficiently discussed or for which current solutions are still limited. In this Perspective, we elaborate on these limitations and suggest points of attention for future research. We finally discuss new opportunities and challenges brought to the field by the rapid development of single-cell high-throughput molecular technologies.
140.
Planell, Nuria; Lagani, Vincenzo; Sebastian-Leon, Patricia; Kloet, Frans; Ewing, Ewoud; Karathanasis, Nestoras; Urdangarin, Arantxa; Arozarena, Imanol; Jagodic, Maja; Tsamardinos, Ioannis; Tarazona, Sonia; Conesa, Ana; Tegner, Jesper; Gomez-Cabrero, David
STATegra: Multi-omics data integration - A conceptual scheme with a bioinformatics pipeline Journal Article
In: Front. Genet., vol. 12, pp. 620453, 2021.
@article{Planell2021-dy,
title = {STATegra: Multi-omics data integration - A conceptual scheme with a bioinformatics pipeline},
author = {Nuria Planell and Vincenzo Lagani and Patricia Sebastian-Leon and Frans Kloet and Ewoud Ewing and Nestoras Karathanasis and Arantxa Urdangarin and Imanol Arozarena and Maja Jagodic and Ioannis Tsamardinos and Sonia Tarazona and Ana Conesa and Jesper Tegner and David Gomez-Cabrero},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970106/pdf/fgene-12-620453.pdf},
doi = {10.3389/fgene.2021.620453},
year = {2021},
date = {2021-03-01},
urldate = {2021-03-01},
journal = {Front. Genet.},
volume = {12},
pages = {620453},
abstract = {Technologies for profiling samples using different omics
platforms have been at the forefront since the human genome
project. Large-scale multi-omics data hold the promise of
deciphering different regulatory layers. Yet, while there is a
myriad of bioinformatics tools, each multi-omics analysis appears
to start from scratch with an arbitrary decision over which tools
to use and how to combine them. Therefore, it is an unmet need to
conceptualize how to integrate such data and implement and
validate pipelines in different cases. We have designed a
conceptual framework (STATegra), aiming it to be as generic as
possible for multi-omics analysis, combining available multi-omic
anlaysis tools (machine learning component analysis,
non-parametric data combination, and a multi-omics exploratory
analysis) in a step-wise manner. While in several studies, we
have previously combined those integrative tools, here, we
provide a systematic description of the STATegra framework and
its validation using two The Cancer Genome Atlas (TCGA) case
studies. For both, the Glioblastoma and the Skin Cutaneous
Melanoma (SKCM) cases, we demonstrate an enhanced capacity of the
framework (and beyond the individual tools) to identify features
and pathways compared to single-omics analysis. Such an
integrative multi-omics analysis framework for identifying
features and components facilitates the discovery of new biology.
Finally, we provide several options for applying the STATegra
framework when parametric assumptions are fulfilled and for the
case when not all the samples are profiled for all omics. The
STATegra framework is built using several tools, which are being
integrated step-by-step as OpenSource in the STATegRa
Bioconductor package.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Technologies for profiling samples using different omics
platforms have been at the forefront since the human genome
project. Large-scale multi-omics data hold the promise of
deciphering different regulatory layers. Yet, while there is a
myriad of bioinformatics tools, each multi-omics analysis appears
to start from scratch with an arbitrary decision over which tools
to use and how to combine them. Therefore, it is an unmet need to
conceptualize how to integrate such data and implement and
validate pipelines in different cases. We have designed a
conceptual framework (STATegra), aiming it to be as generic as
possible for multi-omics analysis, combining available multi-omic
anlaysis tools (machine learning component analysis,
non-parametric data combination, and a multi-omics exploratory
analysis) in a step-wise manner. While in several studies, we
have previously combined those integrative tools, here, we
provide a systematic description of the STATegra framework and
its validation using two The Cancer Genome Atlas (TCGA) case
studies. For both, the Glioblastoma and the Skin Cutaneous
Melanoma (SKCM) cases, we demonstrate an enhanced capacity of the
framework (and beyond the individual tools) to identify features
and pathways compared to single-omics analysis. Such an
integrative multi-omics analysis framework for identifying
features and components facilitates the discovery of new biology.
Finally, we provide several options for applying the STATegra
framework when parametric assumptions are fulfilled and for the
case when not all the samples are profiled for all omics. The
STATegra framework is built using several tools, which are being
integrated step-by-step as OpenSource in the STATegRa
Bioconductor package.
platforms have been at the forefront since the human genome
project. Large-scale multi-omics data hold the promise of
deciphering different regulatory layers. Yet, while there is a
myriad of bioinformatics tools, each multi-omics analysis appears
to start from scratch with an arbitrary decision over which tools
to use and how to combine them. Therefore, it is an unmet need to
conceptualize how to integrate such data and implement and
validate pipelines in different cases. We have designed a
conceptual framework (STATegra), aiming it to be as generic as
possible for multi-omics analysis, combining available multi-omic
anlaysis tools (machine learning component analysis,
non-parametric data combination, and a multi-omics exploratory
analysis) in a step-wise manner. While in several studies, we
have previously combined those integrative tools, here, we
provide a systematic description of the STATegra framework and
its validation using two The Cancer Genome Atlas (TCGA) case
studies. For both, the Glioblastoma and the Skin Cutaneous
Melanoma (SKCM) cases, we demonstrate an enhanced capacity of the
framework (and beyond the individual tools) to identify features
and pathways compared to single-omics analysis. Such an
integrative multi-omics analysis framework for identifying
features and components facilitates the discovery of new biology.
Finally, we provide several options for applying the STATegra
framework when parametric assumptions are fulfilled and for the
case when not all the samples are profiled for all omics. The
STATegra framework is built using several tools, which are being
integrated step-by-step as OpenSource in the STATegRa
Bioconductor package.
139.
Arzalluz-Luque, Angeles; Salguero, Pedro; Tarazona, Sonia; Conesa, Ana
Acorde: unraveling functionally-interpretable networks of isoform co-usage from single cell data Journal Article
In: bioRxiv, 2021.
@article{arzalluz2021acorde,
title = {Acorde: unraveling functionally-interpretable networks of isoform co-usage from single cell data},
author = {Angeles Arzalluz-Luque and Pedro Salguero and Sonia Tarazona and Ana Conesa},
year = {2021},
date = {2021-01-01},
journal = {bioRxiv},
publisher = {Cold Spring Harbor Laboratory},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
138.
Nanni, Adalena V; Morse, Alison M; Newman, Jeremy RB; Choquette, Nicole E; Wedow, Jessica M; Liu, Zihao; Leakey, Andrew DB; Conesa, Ana; Ainsworth, Elizabeth A; McIntyre, Lauren
Ozone sensitivity of diverse maize genotypes is associated with differences in gene regulation, not gene content Journal Article
In: bioRxiv, 2021.
@article{nanni2021ozone,
title = {Ozone sensitivity of diverse maize genotypes is associated with differences in gene regulation, not gene content},
author = {Adalena V Nanni and Alison M Morse and Jeremy RB Newman and Nicole E Choquette and Jessica M Wedow and Zihao Liu and Andrew DB Leakey and Ana Conesa and Elizabeth A Ainsworth and Lauren McIntyre},
year = {2021},
date = {2021-01-01},
journal = {bioRxiv},
publisher = {Cold Spring Harbor Laboratory},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
137.
Puig, Laura Sardón; Altintas, Ali; Casani, Salvador; Gabriel, Brendan M; Barres, Romain; Conesa, Ana; Chibalin, Alexander V; Naslund, Erik; Krook, Anna; Pillon, Nicolas J; others,
Circadian Transcriptomic and Epigenomic Remodeling in Response to Lipid Overload and Human Obesity Journal Article
In: bioRxiv, 2021.
@article{puig2021circadian,
title = {Circadian Transcriptomic and Epigenomic Remodeling in Response to Lipid Overload and Human Obesity},
author = {Laura Sardón Puig and Ali Altintas and Salvador Casani and Brendan M Gabriel and Romain Barres and Ana Conesa and Alexander V Chibalin and Erik Naslund and Anna Krook and Nicolas J Pillon and others},
year = {2021},
date = {2021-01-01},
journal = {bioRxiv},
publisher = {Cold Spring Harbor Laboratory},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
136.
Rubio, Teresa; Felipo, Vicente; Tarazona, Sonia; Pastorelli, Roberta; Escudero-Garc'ia, Desamparados; Tosca, Joan; Urios, Amparo; Conesa, Ana; Montoliu, Carmina
Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients Journal Article
In: Scientific reports, vol. 11, no. 1, pp. 1–14, 2021.
@article{rubio2021multi,
title = {Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients},
author = {Teresa Rubio and Vicente Felipo and Sonia Tarazona and Roberta Pastorelli and Desamparados Escudero-Garc{'i}a and Joan Tosca and Amparo Urios and Ana Conesa and Carmina Montoliu},
year = {2021},
date = {2021-01-01},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {1--14},
publisher = {Nature Publishing Group},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
135.
Balzano-Nogueira, Leandro; Ramirez, Ricardo; Zamkovaya, Tatyana; Dailey, Jordan; Ardissone, Alexandria N; Chamala, Srikar; Serrano-Qu'ilez, Joan; Rubio, Teresa; Haller, Michael J; Concannon, Patrick; others,
Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes Journal Article
In: Genome biology, vol. 22, no. 1, pp. 1–27, 2021.
@article{balzano2021integrative,
title = {Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes},
author = {Leandro Balzano-Nogueira and Ricardo Ramirez and Tatyana Zamkovaya and Jordan Dailey and Alexandria N Ardissone and Srikar Chamala and Joan Serrano-Qu{'i}lez and Teresa Rubio and Michael J Haller and Patrick Concannon and others},
year = {2021},
date = {2021-01-01},
journal = {Genome biology},
volume = {22},
number = {1},
pages = {1--27},
publisher = {BioMed Central},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
134.
Tarazona, Sonia; Carmona, Héctor; Conesa, Ana; Llansola, Marta; Felipo, Vicente
A multi-omic study for uncovering molecular mechanisms associated with hyperammonemia-induced cerebellar function impairment in rats Journal Article
In: Cell Biology and Toxicology, vol. 37, no. 1, pp. 129–149, 2021.
@article{tarazona2021multi,
title = {A multi-omic study for uncovering molecular mechanisms associated with hyperammonemia-induced cerebellar function impairment in rats},
author = {Sonia Tarazona and Héctor Carmona and Ana Conesa and Marta Llansola and Vicente Felipo},
year = {2021},
date = {2021-01-01},
journal = {Cell Biology and Toxicology},
volume = {37},
number = {1},
pages = {129--149},
publisher = {Springer Netherlands},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
133.
Zamkovaya, Tatyana; Foster, Jamie S; de Crécy-Lagard, Valérie; Conesa, Ana
A network approach to elucidate and prioritize microbial dark matter in microbial communities Journal Article
In: The ISME Journal, vol. 15, no. 1, pp. 228–244, 2021.
@article{zamkovaya2021network,
title = {A network approach to elucidate and prioritize microbial dark matter in microbial communities},
author = {Tatyana Zamkovaya and Jamie S Foster and Valérie de Crécy-Lagard and Ana Conesa},
year = {2021},
date = {2021-01-01},
journal = {The ISME Journal},
volume = {15},
number = {1},
pages = {228--244},
publisher = {Nature Publishing Group},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2020
132.
Balzano-Nogueira L Tarazona S, Gómez-Cabrero D
Harmonization of quality metrics and power calculation in multi-omic studies Journal Article
In: Nature Communications, vol. 11, no. 1, pp. 3092, 2020.
@article{S2020,
title = {Harmonization of quality metrics and power calculation in multi-omic studies},
author = {Tarazona S, Balzano-Nogueira L, Gómez-Cabrero D, Schmidt A, Imhof A, Hankemeier T, Tegnér J, Westerhuis JA, Conesa A.},
url = {https://pubmed.ncbi.nlm.nih.gov/32555183/},
doi = {10.1038/s41467-020-16937-8},
year = {2020},
date = {2020-06-18},
journal = {Nature Communications},
volume = {11},
number = {1},
pages = {3092},
abstract = {Multi-omic studies combine measurements at different molecular levels to build comprehensive models of cellular systems. The success of a multi-omic data analysis strategy depends largely on the adoption of adequate experimental designs, and on the quality of the measurements provided by the different omic platforms. However, the field lacks a comparative description of performance parameters across omic technologies and a formulation for experimental design in multi-omic data scenarios. Here, we propose a set of harmonized Figures of Merit (FoM) as quality descriptors applicable to different omic data types. Employing this information, we formulate the MultiPower method to estimate and assess the optimal sample size in a multi-omics experiment. MultiPower supports different experimental settings, data types and sample sizes, and includes graphical for experimental design decision-making. MultiPower is complemented with MultiML, an algorithm to estimate sample size for machine learning classification problems based on multi-omic data.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Multi-omic studies combine measurements at different molecular levels to build comprehensive models of cellular systems. The success of a multi-omic data analysis strategy depends largely on the adoption of adequate experimental designs, and on the quality of the measurements provided by the different omic platforms. However, the field lacks a comparative description of performance parameters across omic technologies and a formulation for experimental design in multi-omic data scenarios. Here, we propose a set of harmonized Figures of Merit (FoM) as quality descriptors applicable to different omic data types. Employing this information, we formulate the MultiPower method to estimate and assess the optimal sample size in a multi-omics experiment. MultiPower supports different experimental settings, data types and sample sizes, and includes graphical for experimental design decision-making. MultiPower is complemented with MultiML, an algorithm to estimate sample size for machine learning classification problems based on multi-omic data.
131.
Ugidos, Manuel; Tarazona, Sonia; Prats-Montalbán, José M; Ferrer, Alberto; Conesa, Ana
MultiBaC: A strategy to remove batch effects between different omic data types Journal Article
In: Statistical Methods in Medical Research, vol. 0, no. 0, pp. 1-14, 2020, (PMID: 32131696).
@article{doi:10.1177/0962280220907365,
title = {MultiBaC: A strategy to remove batch effects between different omic data types},
author = { Manuel Ugidos and Sonia Tarazona and José M Prats-Montalbán and Alberto Ferrer and Ana Conesa},
url = {https://doi.org/10.1177/0962280220907365},
doi = {10.1177/0962280220907365},
year = {2020},
date = {2020-03-05},
journal = {Statistical Methods in Medical Research},
volume = {0},
number = {0},
pages = {1-14},
abstract = {Diversity of omic technologies has expanded in the last years together with the number of omic data integration strategies. However, multiomic data generation is costly, and many research groups cannot afford research projects where many different omic techniques are generated, at least at the same time. As most researchers share their data in public repositories, different omic datasets of the same biological system obtained at different labs can be combined to construct a multiomic study. However, data obtained at different labs or moments in time are typically subjected to batch effects that need to be removed for successful data integration. While there are methods to correct batch effects
on the same data types obtained in different studies, they cannot be applied to correct lab or batch effects across omics. This impairs multiomic meta-analysis. Fortunately, in many cases, at least one omics platform—i.e. gene expression— is repeatedly measured across labs, together with the additional omic modalities that are specific to each study. This
creates an opportunity for batch analysis. We have developed MultiBaC (multiomic Multiomics Batch-effect Correction
correction), a strategy to correct batch effects from multiomic datasets distributed across different labs or data acquisition events. Our strategy is based on the existence of at least one shared data type which allows data prediction across omics. We validate this approach both on simulated data and on a case where the multiomic design is fully shared by two labs, hence batch effect correction within the same omic modality using traditional methods can be compared with the MultiBaC correction across data types. Finally, we apply MultiBaC to a true multiomic data integration problem to show that we are able to improve the detection of meaningful biological effects.},
note = {PMID: 32131696},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Diversity of omic technologies has expanded in the last years together with the number of omic data integration strategies. However, multiomic data generation is costly, and many research groups cannot afford research projects where many different omic techniques are generated, at least at the same time. As most researchers share their data in public repositories, different omic datasets of the same biological system obtained at different labs can be combined to construct a multiomic study. However, data obtained at different labs or moments in time are typically subjected to batch effects that need to be removed for successful data integration. While there are methods to correct batch effects
on the same data types obtained in different studies, they cannot be applied to correct lab or batch effects across omics. This impairs multiomic meta-analysis. Fortunately, in many cases, at least one omics platform—i.e. gene expression— is repeatedly measured across labs, together with the additional omic modalities that are specific to each study. This
creates an opportunity for batch analysis. We have developed MultiBaC (multiomic Multiomics Batch-effect Correction
correction), a strategy to correct batch effects from multiomic datasets distributed across different labs or data acquisition events. Our strategy is based on the existence of at least one shared data type which allows data prediction across omics. We validate this approach both on simulated data and on a case where the multiomic design is fully shared by two labs, hence batch effect correction within the same omic modality using traditional methods can be compared with the MultiBaC correction across data types. Finally, we apply MultiBaC to a true multiomic data integration problem to show that we are able to improve the detection of meaningful biological effects.
on the same data types obtained in different studies, they cannot be applied to correct lab or batch effects across omics. This impairs multiomic meta-analysis. Fortunately, in many cases, at least one omics platform—i.e. gene expression— is repeatedly measured across labs, together with the additional omic modalities that are specific to each study. This
creates an opportunity for batch analysis. We have developed MultiBaC (multiomic Multiomics Batch-effect Correction
correction), a strategy to correct batch effects from multiomic datasets distributed across different labs or data acquisition events. Our strategy is based on the existence of at least one shared data type which allows data prediction across omics. We validate this approach both on simulated data and on a case where the multiomic design is fully shared by two labs, hence batch effect correction within the same omic modality using traditional methods can be compared with the MultiBaC correction across data types. Finally, we apply MultiBaC to a true multiomic data integration problem to show that we are able to improve the detection of meaningful biological effects.
130.
Nuño, Carme; Ugidos, Manuel; Tarazona, Sonia; Martín-Expósito, Manuel; Ferrer, Alberto; Rodríguez-Navarro, Susana; Conesa, Ana
A multi-omics dataset of heat-shock response in the yeast RNA binding protein Mip6 Journal Article
In: Scientific data, vol. 7, no. 1, pp. 69-69, 2020, ISSN: 2052-4463, (32109230[pmid]).
@article{Nuño-Cabanes2020b,
title = {A multi-omics dataset of heat-shock response in the yeast RNA binding protein Mip6},
author = {Carme Nuño and Manuel Ugidos and Sonia Tarazona and Manuel Martín-Expósito and Alberto Ferrer and Susana Rodríguez-Navarro and Ana Conesa},
url = {https://pubmed.ncbi.nlm.nih.gov/32109230},
doi = {10.1038/s41597-020-0412-z},
issn = {2052-4463},
year = {2020},
date = {2020-02-27},
journal = {Scientific data},
volume = {7},
number = {1},
pages = {69-69},
address = {England},
abstract = {Gene expression is a biological process regulated at different molecular levels, including chromatin accessibility, transcription, and RNA maturation and transport. In addition, these regulatory mechanisms have strong links with cellular metabolism. Here we present a multi-omics dataset that captures different aspects of this multi-layered process in yeast. We obtained RNA-seq, metabolomics, and H4K12ac ChIP-seq data for wild-type and mip6D strains during a heat-shock time course. Mip6 is an RNA-binding protein that contributes to RNA export during environmental stress and is informative of the contribution of post-transcriptional regulation to control cellular adaptations to environmental changes. The experiment was performed in quadruplicate, and the different omics measurements were obtained from the same biological samples, which facilitates the integration and analysis of data using covariance-based methods. We validate our dataset by showing that ChIP-seq, RNA-seq and metabolomics signals recapitulate existing knowledge about the response of ribosomal genes and the contribution of trehalose metabolism to heat stress. Raw data, processed data and preprocessing scripts are made available.},
note = {32109230[pmid]},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gene expression is a biological process regulated at different molecular levels, including chromatin accessibility, transcription, and RNA maturation and transport. In addition, these regulatory mechanisms have strong links with cellular metabolism. Here we present a multi-omics dataset that captures different aspects of this multi-layered process in yeast. We obtained RNA-seq, metabolomics, and H4K12ac ChIP-seq data for wild-type and mip6D strains during a heat-shock time course. Mip6 is an RNA-binding protein that contributes to RNA export during environmental stress and is informative of the contribution of post-transcriptional regulation to control cellular adaptations to environmental changes. The experiment was performed in quadruplicate, and the different omics measurements were obtained from the same biological samples, which facilitates the integration and analysis of data using covariance-based methods. We validate our dataset by showing that ChIP-seq, RNA-seq and metabolomics signals recapitulate existing knowledge about the response of ribosomal genes and the contribution of trehalose metabolism to heat stress. Raw data, processed data and preprocessing scripts are made available.
129.
Casan'i-Galdón, Salvador; Pereira, Cecile; Conesa, Ana
Padhoc: a computational pipeline for pathway reconstruction on the fly Journal Article
In: Bioinformatics, vol. 36, no. Supplement_2, pp. i795–i803, 2020.
@article{casani2020padhoc,
title = {Padhoc: a computational pipeline for pathway reconstruction on the fly},
author = {Salvador Casan{'i}-Galdón and Cecile Pereira and Ana Conesa},
year = {2020},
date = {2020-01-01},
journal = {Bioinformatics},
volume = {36},
number = {Supplement_2},
pages = {i795--i803},
publisher = {Oxford University Press},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
128.
Ylla, Guillem; Liu, Tianyuan; Conesa, Ana
MirCure: a tool for quality control, filter and curation of microRNAs of animals and plants Journal Article
In: Bioinformatics, vol. 36, no. Supplement_2, pp. i618–i624, 2020.
@article{ylla2020mircure,
title = {MirCure: a tool for quality control, filter and curation of microRNAs of animals and plants},
author = {Guillem Ylla and Tianyuan Liu and Ana Conesa},
year = {2020},
date = {2020-01-01},
journal = {Bioinformatics},
volume = {36},
number = {Supplement_2},
pages = {i618--i624},
publisher = {Oxford University Press},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
127.
Bhattarai, Krishna; Conesa, Ana; Xiao, Shunyuan; Peres, Natalia A; Clark, David G; Parajuli, Saroj; Deng, Zhanao
Sequencing and analysis of gerbera daisy leaf transcriptomes reveal disease resistance and susceptibility genes differentially expressed and associated with powdery mildew resistance Journal Article
In: BMC plant biology, vol. 20, no. 1, pp. 1–17, 2020.
@article{bhattarai2020sequencing,
title = {Sequencing and analysis of gerbera daisy leaf transcriptomes reveal disease resistance and susceptibility genes differentially expressed and associated with powdery mildew resistance},
author = {Krishna Bhattarai and Ana Conesa and Shunyuan Xiao and Natalia A Peres and David G Clark and Saroj Parajuli and Zhanao Deng},
year = {2020},
date = {2020-01-01},
journal = {BMC plant biology},
volume = {20},
number = {1},
pages = {1--17},
publisher = {BioMed Central},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
126.
Liu, Tianyuan; Balzano-Nogueira, Leandro; Lleo, Ana; Conesa, Ana
Transcriptional differences for COVID-19 Disease Map genes between males and females indicate a different basal immunophenotype relevant to the disease Journal Article
In: Genes, vol. 11, no. 12, pp. 1447, 2020.
@article{liu2020transcriptional,
title = {Transcriptional differences for COVID-19 Disease Map genes between males and females indicate a different basal immunophenotype relevant to the disease},
author = {Tianyuan Liu and Leandro Balzano-Nogueira and Ana Lleo and Ana Conesa},
year = {2020},
date = {2020-01-01},
journal = {Genes},
volume = {11},
number = {12},
pages = {1447},
publisher = {Multidisciplinary Digital Publishing Institute},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
125.
Gardner, Christopher L; da Silva, Danilo R; Pagliai, Fernando A; Pan, Lei; Padgett-Pagliai, Kaylie A; Blaustein, Ryan A; Merli, Marcelo L; Zhang, Dan; Pereira, Cécile; Teplitski, Max; others,
Assessment of unconventional antimicrobial compounds for the control of ‘Candidatus liberibacter asiaticus’, the causative agent of citrus greening disease Journal Article
In: Scientific reports, vol. 10, no. 1, pp. 1–15, 2020.
@article{gardner2020assessment,
title = {Assessment of unconventional antimicrobial compounds for the control of ‘Candidatus liberibacter asiaticus’, the causative agent of citrus greening disease},
author = {Christopher L Gardner and Danilo R da Silva and Fernando A Pagliai and Lei Pan and Kaylie A Padgett-Pagliai and Ryan A Blaustein and Marcelo L Merli and Dan Zhang and Cécile Pereira and Max Teplitski and others},
year = {2020},
date = {2020-01-01},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {1--15},
publisher = {Nature Publishing Group},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
124.
de la Fuente, Lorena; Arzalluz-Luque, Ángeles; Tardáguila, Manuel; Risco, Héctor Del; Mart'i, Cristina; Tarazona, Sonia; Salguero, Pedro; Scott, Raymond; Lerma, Alberto; Alastrue-Agudo, Ana; others,
tappAS: a comprehensive computational framework for the analysis of the functional impact of differential splicing Journal Article
In: Genome biology, vol. 21, pp. 1–32, 2020.
@article{de2020tappas,
title = {tappAS: a comprehensive computational framework for the analysis of the functional impact of differential splicing},
author = {Lorena de la Fuente and Ángeles Arzalluz-Luque and Manuel Tardáguila and Héctor Del Risco and Cristina Mart{'i} and Sonia Tarazona and Pedro Salguero and Raymond Scott and Alberto Lerma and Ana Alastrue-Agudo and others},
url = {https://genomebiology.biomedcentral.com/articles/10.1186/s13059-020-02028-w},
doi = {https://doi.org/10.1186/s13059-020-02028-w},
year = {2020},
date = {2020-01-01},
journal = {Genome biology},
volume = {21},
pages = {1--32},
publisher = {BioMed Central},
abstract = {Recent advances in long-read sequencing solve inaccuracies in alternative transcript identification of full-length transcripts in short-read RNA-Seq data, which encourages the development of methods for isoform-centered functional analysis. Here, we present tappAS, the first framework to enable a comprehensive Functional Iso-Transcriptomics (FIT) analysis, which is effective at revealing the functional impact of context-specific post-transcriptional regulation. tappAS uses isoform-resolved annotation of coding and non-coding functional domains, motifs, and sites, in combination with novel analysis methods to interrogate different aspects of the functional readout of transcript variants and isoform regulation. tappAS software and documentation are available at https://app.tappas.org.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Recent advances in long-read sequencing solve inaccuracies in alternative transcript identification of full-length transcripts in short-read RNA-Seq data, which encourages the development of methods for isoform-centered functional analysis. Here, we present tappAS, the first framework to enable a comprehensive Functional Iso-Transcriptomics (FIT) analysis, which is effective at revealing the functional impact of context-specific post-transcriptional regulation. tappAS uses isoform-resolved annotation of coding and non-coding functional domains, motifs, and sites, in combination with novel analysis methods to interrogate different aspects of the functional readout of transcript variants and isoform regulation. tappAS software and documentation are available at https://app.tappas.org.
2019
123.
Sana, T. G.; Lomas, R.; Gimenez, M. R.; Laubier, A.; Soscia, C.; Chauvet, C.; Conesa, A.; Voulhoux, R.; Ize, B.; Bleves, S.
Differential Modulation of Quorum Sensing Signaling through QslA in Pseudomonas aeruginosa Strains PAO1 and PA14 Journal Article
In: Journal of bacteriology, vol. 201, no. 21, 2019, ISSN: 10985530.
@article{Sana2019,
title = {Differential Modulation of Quorum Sensing Signaling through QslA in Pseudomonas aeruginosa Strains PAO1 and PA14},
author = { T. G. Sana and R. Lomas and M. R. Gimenez and A. Laubier and C. Soscia and C. Chauvet and A. Conesa and R. Voulhoux and B. Ize and S. Bleves},
url = {https://jb.asm.org/content/201/21/e00362-19.abstract},
doi = {10.1128/JB.00362-19},
issn = {10985530},
year = {2019},
date = {2019-11-01},
journal = {Journal of bacteriology},
volume = {201},
number = {21},
publisher = {NLM (Medline)},
abstract = {Two clinical isolates of the opportunist pathogen Pseudomonas aeruginosa named PAO1 and PA14 are commonly studied in research laboratories. Despite the isolates being closely related, PA14 exhibits increased virulence compared to that of PAO1 in various models. To determine which players are responsible for the hypervirulence phenotype of the PA14 strain, we elected a transcriptomic approach through RNA sequencing. We found 2,029 genes that are differentially expressed between the two strains, including several genes that are involved with or regulated by quorum sensing (QS), known to control most of the virulence factors in P. aeruginosa Among them, we chose to focus our study on QslA, an antiactivator of QS whose expression was barely detectable in the PA14 strain according our data. We hypothesized that lack of expression of qslA in PA14 could be responsible for higher QS expression in the PA14 strain, possibly explaining its hypervirulence phenotype. After confirming that QslA protein was highly produced in PAO1 but not in the PA14 strain, we obtained evidence showing that a PAO1 deletion strain of qslA has faster QS gene expression kinetics than PA14. Moreover, known virulence factors activated by QS, such as (i) pyocyanin production, (ii) H2-T6SS (type VI secretion system) gene expression, and (iii) Xcp-T2SS (type II secretion system) machinery production and secretion, were all lower in PAO1 than in PA14, due to higher qslA expression. However, biofilm formation and cytotoxicity toward macrophages, although increased in PA14 compared to PAO1, were independent of QslA control. Together, our findings implicated differential qslA expression as a major determinant of virulence factor expression in P. aeruginosa strains PAO1 and PA14.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen responsible for acute nosocomial infections and chronic pulmonary infections. P. aeruginosa strain PA14 is known to be hypervirulent in different hosts. Despite several studies in the field, the underlining molecular mechanisms sustaining this phenotype remain enigmatic. Here we provide evidence that the PA14 strain has faster quorum sensing (QS) kinetics than the PAO1 strain, due to the lack of QslA expression, an antiactivator of QS. QS is a major regulator of virulence factors in P. aeruginosa; therefore, we propose that the hypervirulent phenotype of the PA14 strain is, at least partially, due to the lack of QslA expression. This mechanism could be of great importance, as it could be conserved among other P. aeruginosa isolates.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Two clinical isolates of the opportunist pathogen Pseudomonas aeruginosa named PAO1 and PA14 are commonly studied in research laboratories. Despite the isolates being closely related, PA14 exhibits increased virulence compared to that of PAO1 in various models. To determine which players are responsible for the hypervirulence phenotype of the PA14 strain, we elected a transcriptomic approach through RNA sequencing. We found 2,029 genes that are differentially expressed between the two strains, including several genes that are involved with or regulated by quorum sensing (QS), known to control most of the virulence factors in P. aeruginosa Among them, we chose to focus our study on QslA, an antiactivator of QS whose expression was barely detectable in the PA14 strain according our data. We hypothesized that lack of expression of qslA in PA14 could be responsible for higher QS expression in the PA14 strain, possibly explaining its hypervirulence phenotype. After confirming that QslA protein was highly produced in PAO1 but not in the PA14 strain, we obtained evidence showing that a PAO1 deletion strain of qslA has faster QS gene expression kinetics than PA14. Moreover, known virulence factors activated by QS, such as (i) pyocyanin production, (ii) H2-T6SS (type VI secretion system) gene expression, and (iii) Xcp-T2SS (type II secretion system) machinery production and secretion, were all lower in PAO1 than in PA14, due to higher qslA expression. However, biofilm formation and cytotoxicity toward macrophages, although increased in PA14 compared to PAO1, were independent of QslA control. Together, our findings implicated differential qslA expression as a major determinant of virulence factor expression in P. aeruginosa strains PAO1 and PA14.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen responsible for acute nosocomial infections and chronic pulmonary infections. P. aeruginosa strain PA14 is known to be hypervirulent in different hosts. Despite several studies in the field, the underlining molecular mechanisms sustaining this phenotype remain enigmatic. Here we provide evidence that the PA14 strain has faster quorum sensing (QS) kinetics than the PAO1 strain, due to the lack of QslA expression, an antiactivator of QS. QS is a major regulator of virulence factors in P. aeruginosa; therefore, we propose that the hypervirulent phenotype of the PA14 strain is, at least partially, due to the lack of QslA expression. This mechanism could be of great importance, as it could be conserved among other P. aeruginosa isolates.
122.
Jansen, Camden; Ramirez, Ricardo N; El-Ali, Nicole C; Gomez-Cabrero, David; Tegner, Jesper; Merkenschlager, Matthias; Conesa, Ana; Mortazavi, Ali
Building gene regulatory networks from scATAC-seq and scRNA-seq using Linked Self Organizing Maps Journal Article
In: PLOS Computational Biology, vol. 15, no. 11, pp. e1006555, 2019, ISSN: 1553-7358.
@article{Jansen2019b,
title = {Building gene regulatory networks from scATAC-seq and scRNA-seq using Linked Self Organizing Maps},
author = {Camden Jansen and Ricardo N Ramirez and Nicole C El-Ali and David Gomez-Cabrero and Jesper Tegner and Matthias Merkenschlager and Ana Conesa and Ali Mortazavi},
editor = {Christina S Leslie},
url = {https://dx.plos.org/10.1371/journal.pcbi.1006555},
doi = {10.1371/journal.pcbi.1006555},
issn = {1553-7358},
year = {2019},
date = {2019-11-01},
journal = {PLOS Computational Biology},
volume = {15},
number = {11},
pages = {e1006555},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
121.
Martín‐Expósito, Manuel; Gas, Maria‐Eugenia; Mohamad, Nada; Nuño‐Cabanes, Carme; Tejada‐Colón, Ana; Pascual‐García, Pau; Fuente, Lorena; Chaves‐Arquero, Belén; Merran, Jonathan; Corden, Jeffry; Conesa, Ana; Pérez‐Cañadillas, José Manuel; Bravo, Jerónimo; Rodríguez‐Navarro, Susana
Mip6 binds directly to the Mex67 UBA domain to maintain low levels of Msn2/4 stress‐dependent mRNAs Journal Article
In: EMBO reports, 2019, ISSN: 1469-221X.
@article{MartinExposito2019,
title = {Mip6 binds directly to the Mex67 UBA domain to maintain low levels of Msn2/4 stress‐dependent mRNAs},
author = { Manuel Martín‐Expósito and Maria‐Eugenia Gas and Nada Mohamad and Carme Nuño‐Cabanes and Ana Tejada‐Colón and Pau Pascual‐García and Lorena Fuente and Belén Chaves‐Arquero and Jonathan Merran and Jeffry Corden and Ana Conesa and José Manuel Pérez‐Cañadillas and Jerónimo Bravo and Susana Rodríguez‐Navarro},
url = {https://onlinelibrary.wiley.com/doi/abs/10.15252/embr.201947964},
doi = {10.15252/embr.201947964},
issn = {1469-221X},
year = {2019},
date = {2019-10-29},
journal = {EMBO reports},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
120.
Tarazona, Sonia; Bernabeu, Elena; Carmona, Héctor; Gómez-Giménez, Belén; García-Planells, Javier; Leonards, Pim E. G.; Jung, Stephan; Conesa, Ana; Felipo, Vicente; Llansola, Marta
A Multiomics Study to Unravel the Effects of Developmental Exposure to Endosulfan in Rats: Molecular Explanation for Sex-Dependent Effects Journal Article
In: ACS Chemical Neuroscience, vol. 10, no. 10, pp. 4264–4279, 2019, ISSN: 19487193.
@article{Tarazona2019,
title = {A Multiomics Study to Unravel the Effects of Developmental Exposure to Endosulfan in Rats: Molecular Explanation for Sex-Dependent Effects},
author = { Sonia Tarazona and Elena Bernabeu and Héctor Carmona and Belén Gómez-Giménez and Javier García-Planells and Pim E.G. Leonards and Stephan Jung and Ana Conesa and Vicente Felipo and Marta Llansola},
url = {https://www.ncbi.nlm.nih.gov/pubmed/31464424},
doi = {10.1021/acschemneuro.9b00304},
issn = {19487193},
year = {2019},
date = {2019-10-01},
journal = {ACS Chemical Neuroscience},
volume = {10},
number = {10},
pages = {4264--4279},
publisher = {American Chemical Society},
abstract = {Exposure to low levels of environmental contaminants, including pesticides, induces neurodevelopmental toxicity. Environmental and food contaminants can reach the brain of the fetus, affecting brain development and leading to neurological dysfunction. The pesticide endosulfan is a persistent pollutant, and significant levels still remain detectable in the environment although its use is banned in some countries. In rats, endosulfan exposure during brain development alters motor activity, coordination, learning, and memory, even several months after uptake, and does so in a sex-dependent way. However, the molecular mechanisms driving these effects have not been studied in detail. In this work, we performed a multiomics study in cerebellum from rats exposed to endosulfan during embryonic development. Pregnant rats were orally exposed to a low dose (0.5 mg/kg) of endosulfan, daily, from gestational day 7 to postnatal day 21. The progeny was evaluated for cognitive and motor functions at adulthood. Expression of messenger RNA and microRNA genes, as well as protein and metabolite levels, were measured on cerebellar samples from males and females. An integrative analysis was conducted to identify altered processes under endosulfan effect. Effects between males and females were compared. Pathways significantly altered by endosulfan exposure included the phosphatidylinositol signaling system, calcium signaling, the cGMP-PKG pathway, the inflammatory and immune system, protein processing in the endoplasmic reticulum, and GABA and taurine metabolism. Sex-dependent effects of endosulfan in the omics results that matched sex differences in cognitive and motor tests were found. These results shed light on the molecular basis of impaired neurodevelopment and contribute to the identification of new biomarkers of neurotoxicity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Exposure to low levels of environmental contaminants, including pesticides, induces neurodevelopmental toxicity. Environmental and food contaminants can reach the brain of the fetus, affecting brain development and leading to neurological dysfunction. The pesticide endosulfan is a persistent pollutant, and significant levels still remain detectable in the environment although its use is banned in some countries. In rats, endosulfan exposure during brain development alters motor activity, coordination, learning, and memory, even several months after uptake, and does so in a sex-dependent way. However, the molecular mechanisms driving these effects have not been studied in detail. In this work, we performed a multiomics study in cerebellum from rats exposed to endosulfan during embryonic development. Pregnant rats were orally exposed to a low dose (0.5 mg/kg) of endosulfan, daily, from gestational day 7 to postnatal day 21. The progeny was evaluated for cognitive and motor functions at adulthood. Expression of messenger RNA and microRNA genes, as well as protein and metabolite levels, were measured on cerebellar samples from males and females. An integrative analysis was conducted to identify altered processes under endosulfan effect. Effects between males and females were compared. Pathways significantly altered by endosulfan exposure included the phosphatidylinositol signaling system, calcium signaling, the cGMP-PKG pathway, the inflammatory and immune system, protein processing in the endoplasmic reticulum, and GABA and taurine metabolism. Sex-dependent effects of endosulfan in the omics results that matched sex differences in cognitive and motor tests were found. These results shed light on the molecular basis of impaired neurodevelopment and contribute to the identification of new biomarkers of neurotoxicity.
119.
Gomez-Cabrero, David; Tarazona, Sonia; Ferreirós-Vidal, Isabel; Ramirez, Ricardo N.; Company, Carlos; Schmidt, Andreas; Reijmers, Theo; von Saint Paul, Veronica; Marabita, Francesco; Rodríguez-Ubreva, Javier; Garcia-Gomez, Antonio; Carroll, Thomas; Cooper, Lee; Liang, Ziwei; Dharmalingam, Gopuraja; van der Kloet, Frans; Harms, Amy C.; Balzano-Nogueira, Leandro; Lagani, Vincenzo; Tsamardinos, Ioannis; Lappe, Michael; Maier, Dieter; Westerhuis, Johan A.; Hankemeier, Thomas; Imhof, Axel; Ballestar, Esteban; Mortazavi, Ali; Merkenschlager, Matthias; Tegner, Jesper; Conesa, Ana
STATegra, a comprehensive multi-omics dataset of B-cell differentiation in mouse Journal Article
In: Scientific data, vol. 6, no. 1, pp. 256, 2019, ISSN: 20524463.
@article{Gomez-Cabrero2019,
title = {STATegra, a comprehensive multi-omics dataset of B-cell differentiation in mouse},
author = { David Gomez-Cabrero and Sonia Tarazona and Isabel Ferreirós-Vidal and Ricardo N. Ramirez and Carlos Company and Andreas Schmidt and Theo Reijmers and Veronica von Saint Paul and Francesco Marabita and Javier Rodríguez-Ubreva and Antonio Garcia-Gomez and Thomas Carroll and Lee Cooper and Ziwei Liang and Gopuraja Dharmalingam and Frans van der Kloet and Amy C. Harms and Leandro Balzano-Nogueira and Vincenzo Lagani and Ioannis Tsamardinos and Michael Lappe and Dieter Maier and Johan A. Westerhuis and Thomas Hankemeier and Axel Imhof and Esteban Ballestar and Ali Mortazavi and Matthias Merkenschlager and Jesper Tegner and Ana Conesa},
url = {https://www.nature.com/articles/s41597-019-0202-7},
doi = {10.1038/s41597-019-0202-7},
issn = {20524463},
year = {2019},
date = {2019-10-01},
journal = {Scientific data},
volume = {6},
number = {1},
pages = {256},
publisher = {NLM (Medline)},
abstract = {Multi-omics approaches use a diversity of high-throughput technologies to profile the different molecular layers of living cells. Ideally, the integration of this information should result in comprehensive systems models of cellular physiology and regulation. However, most multi-omics projects still include a limited number of molecular assays and there have been very few multi-omic studies that evaluate dynamic processes such as cellular growth, development and adaptation. Hence, we lack formal analysis methods and comprehensive multi-omics datasets that can be leveraged to develop true multi-layered models for dynamic cellular systems. Here we present the STATegra multi-omics dataset that combines measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation. STATegra includes high-throughput measurements of chromatin structure, gene expression, proteomics and metabolomics, and it is complemented with single-cell data. To our knowledge, the STATegra collection is the most diverse multi-omics dataset describing a dynamic biological system.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Multi-omics approaches use a diversity of high-throughput technologies to profile the different molecular layers of living cells. Ideally, the integration of this information should result in comprehensive systems models of cellular physiology and regulation. However, most multi-omics projects still include a limited number of molecular assays and there have been very few multi-omic studies that evaluate dynamic processes such as cellular growth, development and adaptation. Hence, we lack formal analysis methods and comprehensive multi-omics datasets that can be leveraged to develop true multi-layered models for dynamic cellular systems. Here we present the STATegra multi-omics dataset that combines measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation. STATegra includes high-throughput measurements of chromatin structure, gene expression, proteomics and metabolomics, and it is complemented with single-cell data. To our knowledge, the STATegra collection is the most diverse multi-omics dataset describing a dynamic biological system.
118.
García-Solano, José; del Carmen Turpin-Sevilla, María; García-García, Francisco; Carbonell-Muñoz, Rosa; Torres-Moreno, Daniel; Conesa, Ana; Conesa-Zamora, Pablo
Differences in gene expression profiling and biomarkers between histological colorectal carcinoma subsets from the serrated pathway Journal Article
In: Histopathology, vol. 75, no. 4, pp. 496–507, 2019, ISSN: 13652559.
@article{Garcia-Solano2019,
title = {Differences in gene expression profiling and biomarkers between histological colorectal carcinoma subsets from the serrated pathway},
author = { José García-Solano and María del Carmen Turpin-Sevilla and Francisco García-García and Rosa Carbonell-Muñoz and Daniel Torres-Moreno and Ana Conesa and Pablo Conesa-Zamora},
url = {https://www.ncbi.nlm.nih.gov/pubmed/31025430},
doi = {10.1111/his.13889},
issn = {13652559},
year = {2019},
date = {2019-10-01},
journal = {Histopathology},
volume = {75},
number = {4},
pages = {496--507},
publisher = {Blackwell Publishing Ltd},
abstract = {Aims: To discern the differences in expression profiling of two histological subtypes of colorectal carcinoma (CRC) arising from the serrated route (serrated adenocarcinoma (SAC) and CRC showing histological and molecular features of a high level of microsatellite instability (hmMSI-H) both sharing common features (female gender, right-sided location, mucinous histology, and altered CpG methylation), but dramatically differing in terms of prognosis, development of an immune response, and treatment options. Methods and results: Molecular signatures of SAC and hmMSI-H were obtained by the use of transcriptomic arrays; quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were used to validate differentially expressed genes. An over-representation of innate immunity functions (granulomonocytic recruitment, chemokine production, Toll-like receptor signalling, and antigen processing and presentation) was obtained from this comparison, and intercellular cell adhesion molecule-1 (ICAM1) was more highly expressed in hmMSI-H, whereas two genes [those encoding calcitonin gene-related peptide-receptor component protein and C-X-C motif chemokine ligand 14 (CXCL14)] were more highly expressed in SAC. These array results were subsequently validated by qPCR, and by IHC for CXCL14 and ICAM1. Information retrieved from public databanks confirmed our findings. Conclusions: Our findings highlight specific functions and genes that provide a better understanding of the role of the immune response in the serrated pathological route and may be of help in identifying actionable molecules.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Aims: To discern the differences in expression profiling of two histological subtypes of colorectal carcinoma (CRC) arising from the serrated route (serrated adenocarcinoma (SAC) and CRC showing histological and molecular features of a high level of microsatellite instability (hmMSI-H) both sharing common features (female gender, right-sided location, mucinous histology, and altered CpG methylation), but dramatically differing in terms of prognosis, development of an immune response, and treatment options. Methods and results: Molecular signatures of SAC and hmMSI-H were obtained by the use of transcriptomic arrays; quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were used to validate differentially expressed genes. An over-representation of innate immunity functions (granulomonocytic recruitment, chemokine production, Toll-like receptor signalling, and antigen processing and presentation) was obtained from this comparison, and intercellular cell adhesion molecule-1 (ICAM1) was more highly expressed in hmMSI-H, whereas two genes [those encoding calcitonin gene-related peptide-receptor component protein and C-X-C motif chemokine ligand 14 (CXCL14)] were more highly expressed in SAC. These array results were subsequently validated by qPCR, and by IHC for CXCL14 and ICAM1. Information retrieved from public databanks confirmed our findings. Conclusions: Our findings highlight specific functions and genes that provide a better understanding of the role of the immune response in the serrated pathological route and may be of help in identifying actionable molecules.
117.
Conesa, Ana; Beck, Stephan
Making multi-omics data accessible to researchers Journal Article
In: Scientific data, vol. 6, no. 1, pp. 251, 2019, ISSN: 20524463.
@article{Conesa2019,
title = {Making multi-omics data accessible to researchers},
author = { Ana Conesa and Stephan Beck},
url = {https://www.nature.com/articles/s41597-019-0258-4},
doi = {10.1038/s41597-019-0258-4},
issn = {20524463},
year = {2019},
date = {2019-10-01},
journal = {Scientific data},
volume = {6},
number = {1},
pages = {251},
publisher = {NLM (Medline)},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
116.
Ferreirós-Vidal, Isabel; Carroll, Thomas; Zhang, Tianyi; Lagani, Vincenzo; Ramirez, Ricardo N.; Ing-Simmons, Elizabeth; Gómez-Valadés, Alicia G.; Cooper, Lee; Liang, Ziwei; Papoutsoglou, Georgios; Dharmalingam, Gopuraja; Guo, Ya; Tarazona, Sonia; Fernandes, Sunjay J.; Noori, Peri; Silberberg, Gilad; Fisher, Amanda G.; Tsamardinos, Ioannis; Mortazavi, Ali; Lenhard, Boris; Conesa, Ana; Tegner, Jesper; Merkenschlager, Matthias; Gomez-Cabrero, David
Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation Journal Article
In: PLoS Biology, vol. 17, no. 4, 2019, ISSN: 15457885.
@article{Ferreiros-Vidal2019,
title = {Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation},
author = { Isabel Ferreirós-Vidal and Thomas Carroll and Tianyi Zhang and Vincenzo Lagani and Ricardo N. Ramirez and Elizabeth Ing-Simmons and Alicia G. Gómez-Valadés and Lee Cooper and Ziwei Liang and Georgios Papoutsoglou and Gopuraja Dharmalingam and Ya Guo and Sonia Tarazona and Sunjay J. Fernandes and Peri Noori and Gilad Silberberg and Amanda G. Fisher and Ioannis Tsamardinos and Ali Mortazavi and Boris Lenhard and Ana Conesa and Jesper Tegner and Matthias Merkenschlager and David Gomez-Cabrero},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2006506},
doi = {10.1371/journal.pbio.2006506},
issn = {15457885},
year = {2019},
date = {2019-01-01},
journal = {PLoS Biology},
volume = {17},
number = {4},
publisher = {Public Library of Science},
abstract = {The differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage–specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell type–specific genes is an important question, because dissociation between differentiation, cell cycle, and metabolic states is a hallmark of cancer. Here, we use a model system to systematically identify key transcriptional regulators of Ikaros-dependent B cell–progenitor differentiation. We find that the coordinated regulation of housekeeping functions and tissue-specific gene expression requires a feedforward circuit whereby Ikaros down-regulates the expression of Myc. Our findings show how coordination between differentiation and housekeeping states can be achieved by interconnected regulators. Similar principles likely coordinate differentiation and housekeeping functions during progenitor cell differentiation in other cell lineages.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage–specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell type–specific genes is an important question, because dissociation between differentiation, cell cycle, and metabolic states is a hallmark of cancer. Here, we use a model system to systematically identify key transcriptional regulators of Ikaros-dependent B cell–progenitor differentiation. We find that the coordinated regulation of housekeeping functions and tissue-specific gene expression requires a feedforward circuit whereby Ikaros down-regulates the expression of Myc. Our findings show how coordination between differentiation and housekeeping states can be achieved by interconnected regulators. Similar principles likely coordinate differentiation and housekeeping functions during progenitor cell differentiation in other cell lineages.
115.
Brown, Peter; Conesa), RELISH Consortium (Ana; Zhou, Yaoqi
Large expert-curated database for benchmarking document similarity detection in biomedical literature search Journal Article
In: Database, vol. 2019, 2019, ISSN: 1758-0463, (baz085).
@article{10.1093/database/baz085,
title = {Large expert-curated database for benchmarking document similarity detection in biomedical literature search},
author = { Peter Brown and RELISH Consortium (Ana Conesa) and Yaoqi Zhou},
url = {https://doi.org/10.1093/database/baz085},
doi = {10.1093/database/baz085},
issn = {1758-0463},
year = {2019},
date = {2019-01-01},
journal = {Database},
volume = {2019},
abstract = {Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.},
note = {baz085},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.
2018
114.
Duscher, Alexandrea A; Conesa, Ana; Bishop, Mary; Vroom, Madeline M; Zubizarreta, Sergio D; Foster, Jamie S
Transcriptional profiling of the mutualistic bacterium Vibrio fischeri and an hfq mutant under modeled microgravity Journal Article
In: npj Microgravity, vol. 4, no. 1, pp. 25, 2018.
@article{duscher2018transcriptional,
title = {Transcriptional profiling of the mutualistic bacterium Vibrio fischeri and an hfq mutant under modeled microgravity},
author = { Alexandrea A Duscher and Ana Conesa and Mary Bishop and Madeline M Vroom and Sergio D Zubizarreta and Jamie S Foster},
url = {https://doi.org/10.1038/s41526-018-0060-1},
doi = {10.1038/s41526-018-0060-1},
year = {2018},
date = {2018-12-18},
journal = {npj Microgravity},
volume = {4},
number = {1},
pages = {25},
publisher = {Nature Publishing Group},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
113.
Sánchez-Gaya, Víctor; Casaní-Galdón, Salvador; Ugidos, Manuel; Kuang, Zheng; Mellor, Jane; Conesa, Ana; Tarazona, Sonia
In: Frontiers in Genetics, vol. 9, pp. 578, 2018, ISSN: 1664-8021.
@article{10.3389/fgene.2018.00578,
title = {Elucidating the Role of Chromatin State and Transcription Factors on the Regulation of the Yeast Metabolic Cycle: A Multi-Omic Integrative Approach},
author = {Víctor Sánchez-Gaya and Salvador Casaní-Galdón and Manuel Ugidos and Zheng Kuang and Jane Mellor and Ana Conesa and Sonia Tarazona},
url = {https://www.frontiersin.org/article/10.3389/fgene.2018.00578},
doi = {10.3389/fgene.2018.00578},
issn = {1664-8021},
year = {2018},
date = {2018-11-30},
journal = {Frontiers in Genetics},
volume = {9},
pages = {578},
abstract = {The Yeast Metabolic Cycle (YMC) is a model system in which levels of around 60% of the yeast transcripts cycle over time. The spatial and temporal resolution provided by the YMC has revealed that changes in the yeast metabolic landscape and chromatin status can be related to cycling gene expression. However, the interplay between histone modifications and transcription factor activity during the YMC is still poorly understood. Here we apply an innovative statistical approach to integrate chromatin state (ChIP-seq) and gene expression (RNA-seq) data to investigate the transcriptional control during the YMC. By using the multivariate regression models N-PLS (Partial Least Squares) and MORE (Multi-Omics REgulation) methodologies, we assess the contribution of histone marks and transcription factors to the regulation of gene expression in the YMC. We found that H3K18ac and H3K9ac were the most important histone modifications, whereas Sfp1, Hfi1, Pip2, Mig2 and Yhp1 emerged as the most relevant transcription factors. A significant association in the co-regulation of gene expression was found between H3K18ac and the transcription factors Pip2 (involved in fatty acids metabolism), Xbp1 (cyclin implicated in the regulation of carbohydrate and amino acid metabolism), and Hfi1 (involved in the formation of the SAGA complex). These results evidence the crucial role of histone lysine acetylation levels in the regulation of gene expression in the YMC through the coordinated action of transcription factors and lysine acetyl transferases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The Yeast Metabolic Cycle (YMC) is a model system in which levels of around 60% of the yeast transcripts cycle over time. The spatial and temporal resolution provided by the YMC has revealed that changes in the yeast metabolic landscape and chromatin status can be related to cycling gene expression. However, the interplay between histone modifications and transcription factor activity during the YMC is still poorly understood. Here we apply an innovative statistical approach to integrate chromatin state (ChIP-seq) and gene expression (RNA-seq) data to investigate the transcriptional control during the YMC. By using the multivariate regression models N-PLS (Partial Least Squares) and MORE (Multi-Omics REgulation) methodologies, we assess the contribution of histone marks and transcription factors to the regulation of gene expression in the YMC. We found that H3K18ac and H3K9ac were the most important histone modifications, whereas Sfp1, Hfi1, Pip2, Mig2 and Yhp1 emerged as the most relevant transcription factors. A significant association in the co-regulation of gene expression was found between H3K18ac and the transcription factors Pip2 (involved in fatty acids metabolism), Xbp1 (cyclin implicated in the regulation of carbohydrate and amino acid metabolism), and Hfi1 (involved in the formation of the SAGA complex). These results evidence the crucial role of histone lysine acetylation levels in the regulation of gene expression in the YMC through the coordinated action of transcription factors and lysine acetyl transferases.
112.
Solano, José García; Turpin, María C.; Torres-Moreno, Daniel; Huertas-López, Francisco; Tuomisto, Anne; Mäkinen, Markus J.; Conesa, Ana; Conesa-Zamora, Pablo
Two histologically colorectal carcinomas subsets from the serrated pathway show different methylome signatures and diagnostic biomarkers Journal Article
In: Clinical Epigenetics, vol. 10, no. 1, pp. 141, 2018, ISSN: 1868-7083.
@article{García-Solano2018,
title = {Two histologically colorectal carcinomas subsets from the serrated pathway show different methylome signatures and diagnostic biomarkers},
author = {José García Solano and María C. Turpin and Daniel Torres-Moreno and Francisco Huertas-López and Anne Tuomisto and Markus J. Mäkinen and Ana Conesa and Pablo Conesa-Zamora},
url = {https://doi.org/10.1186/s13148-018-0571-3},
doi = {10.1186/s13148-018-0571-3},
issn = {1868-7083},
year = {2018},
date = {2018-11-09},
journal = {Clinical Epigenetics},
volume = {10},
number = {1},
pages = {141},
abstract = {Altered methylation patterns are driving forces in colorectal carcinogenesis. The serrated adenocarcinoma (SAC) and sporadic colorectal carcinoma showing histological and molecular features of microsatellite instability (hmMSI-H) are two endpoints of the so-called serrated pathological route sharing some characteristics but displaying a totally different immune response and clinical outcome. However, there are no studies comparing the methylome of these two subtypes of colorectal carcinomas. The methylation status of 450,000 CpG sites using the Infinium Human Methylation 450 BeadChip array was investigated in 48 colorectal specimens, including 39 SACs and 9 matched hmMSI-H.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Altered methylation patterns are driving forces in colorectal carcinogenesis. The serrated adenocarcinoma (SAC) and sporadic colorectal carcinoma showing histological and molecular features of microsatellite instability (hmMSI-H) are two endpoints of the so-called serrated pathological route sharing some characteristics but displaying a totally different immune response and clinical outcome. However, there are no studies comparing the methylome of these two subtypes of colorectal carcinomas. The methylation status of 450,000 CpG sites using the Infinium Human Methylation 450 BeadChip array was investigated in 48 colorectal specimens, including 39 SACs and 9 matched hmMSI-H.
111.
Fábregas, Norma; Lozano-Elena, Fidel; Blasco-Escámez, David; Tohge, Takayuki; Martínez-Andújar, Cristina; Albacete, Alfonso; Osorio, Sonia; Bustamante, Mariana; Riechmann, José Luis; Nomura, Takahito; Conesa, Takao Yokota Ana; Alfocea, Francisco Pérez; Alisdair R. Fernie, 2; Caño-Delgado, Ana I.
Overexpression of the vascular brassinosteroid receptor BRL3 confers drought resistance without penalizing plant growth Journal Article
In: Nature communications, vol. 9, no. 1, pp. 4680, 2018.
@article{fabregas2018overexpression,
title = {Overexpression of the vascular brassinosteroid receptor BRL3 confers drought resistance without penalizing plant growth},
author = {Norma Fábregas and Fidel Lozano-Elena and David Blasco-Escámez and Takayuki Tohge and Cristina Martínez-Andújar and Alfonso Albacete and Sonia Osorio and Mariana Bustamante and José Luis Riechmann and Takahito Nomura and Takao Yokota Ana Conesa and Francisco Pérez Alfocea and Alisdair R. Fernie,2 and Ana I. Caño-Delgado},
url = {https://doi.org/10.1038/s41467-018-06861-3},
doi = {10.1038/s41467-018-06861-3},
year = {2018},
date = {2018-11-08},
journal = {Nature communications},
volume = {9},
number = {1},
pages = {4680},
publisher = {Nature Publishing Group},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
110.
Tríbulo, Paula; Balzano-Nogueira, Leandro; Conesa, Ana; Siqueira, Luiz G.; Hansen, Peter J.
Changes in the uterine metabolome of the cow during the first seven days after estrus Journal Article
In: Molecular Reproduction and Development, vol. 0, no. ja, 2018.
@article{doi:10.1002/mrd.23082,
title = {Changes in the uterine metabolome of the cow during the first seven days after estrus},
author = { Paula Tríbulo and Leandro Balzano-Nogueira and Ana Conesa and Luiz G. Siqueira and Peter J. Hansen},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/mrd.23082},
doi = {10.1002/mrd.23082},
year = {2018},
date = {2018-11-01},
journal = {Molecular Reproduction and Development},
volume = {0},
number = {ja},
abstract = {Abstract The uterine microenvironment during the first 7 days after ovulation accommodates and facilitates sperm transit to the oviduct and constitutes the sole source of nutrients required for development of preimplantation embryos. Knowledge of the composition of uterine fluid is largely incomplete. Using untargeted mass spectrometry, we characterized the uterine metabolome during the first 7 days of the estrous cycle. Bovine uteri were collected on day 0 (N=4), 3 (N=4), 5 (N=3) and 7 (N=4) relative to ovulation and flushed with Dulbecco’s phosphate-buffered saline. A total of 1,993 molecular features were detected of which 184 peaks with putative identification represent 147 unique metabolites, including amino acids, benzoic acids, lipid molecules, carbohydrates, purines, pyrimidines, vitamins, and other intermediate and secondary metabolites. Results revealed changes in the uterine metabolome as the cow transitions from ovulation to day 7 of the estrous cycle. The majority of metabolites reached maximum intensity on either day 5 or day 7 relative to ovulation. Moreover, several metabolites found in uterine fluid have signaling capabilities and some have been shown to affect preimplantation embryonic development. In conclusion, the metabolome of the bovine uterus changes during early stages of the estrous cycle and is likely to participate in the regulation of preimplantation embryonic development. Data reported here will serve as basis for future studies aiming to evaluate maternal regulation of preimplantation embryonic development and optimal conditions for culture of embryos. This article is protected by copyright. All rights reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Abstract The uterine microenvironment during the first 7 days after ovulation accommodates and facilitates sperm transit to the oviduct and constitutes the sole source of nutrients required for development of preimplantation embryos. Knowledge of the composition of uterine fluid is largely incomplete. Using untargeted mass spectrometry, we characterized the uterine metabolome during the first 7 days of the estrous cycle. Bovine uteri were collected on day 0 (N=4), 3 (N=4), 5 (N=3) and 7 (N=4) relative to ovulation and flushed with Dulbecco’s phosphate-buffered saline. A total of 1,993 molecular features were detected of which 184 peaks with putative identification represent 147 unique metabolites, including amino acids, benzoic acids, lipid molecules, carbohydrates, purines, pyrimidines, vitamins, and other intermediate and secondary metabolites. Results revealed changes in the uterine metabolome as the cow transitions from ovulation to day 7 of the estrous cycle. The majority of metabolites reached maximum intensity on either day 5 or day 7 relative to ovulation. Moreover, several metabolites found in uterine fluid have signaling capabilities and some have been shown to affect preimplantation embryonic development. In conclusion, the metabolome of the bovine uterus changes during early stages of the estrous cycle and is likely to participate in the regulation of preimplantation embryonic development. Data reported here will serve as basis for future studies aiming to evaluate maternal regulation of preimplantation embryonic development and optimal conditions for culture of embryos. This article is protected by copyright. All rights reserved.
109.
Sánchez-Gaya, Víctor; Casaní-Galdón, Salvador; Ugidos, Manuel; Kuang, Zheng; Mellor, Jane; Conesa, Ana; Tarazona, Sonia
In: Frontiers in Genetics, vol. 9, 2018, ISSN: 1664-8021.
@article{Sanchez-Gaya2018,
title = {Elucidating the Role of Chromatin State and Transcription Factors on the Regulation of the Yeast Metabolic Cycle: A Multi-Omic Integrative Approach},
author = {Víctor Sánchez-Gaya and Salvador Casaní-Galdón and Manuel Ugidos and Zheng Kuang and Jane Mellor and Ana Conesa and Sonia Tarazona},
doi = {10.3389/fgene.2018.00578},
issn = {1664-8021},
year = {2018},
date = {2018-11-01},
journal = {Frontiers in Genetics},
volume = {9},
publisher = {Frontiers Media SA},
abstract = {The Yeast Metabolic Cycle (YMC) is a model system in which levels of around 60% of the yeast transcripts cycle over time. The spatial and temporal resolution provided by the YMC has revealed that changes in the yeast metabolic landscape and chromatin status can be related to cycling gene expression. However, the interplay between histone modifications and transcription factor activity during the YMC is still poorly understood. Here we apply an innovative statistical approach to integrate chromatin state (ChIP-seq) and gene expression (RNA-seq) data to investigate the transcriptional control during the YMC. By using the multivariate regression models N-PLS (Partial Least Squares) and MORE (Multi-Omics REgulation) methodologies, we assessed the contribution of histone marks and transcription factors to the regulation of gene expression in the YMC. We found that H3K18ac and H3K9ac were the most important histone modifications, whereas Sfp1, Hfi1, Pip2, Mig2, and Yhp1 emerged as the most relevant transcription factors. A significant association in the co-regulation of gene expression was found between H3K18ac and the transcription factors Pip2 (involved in fatty acids metabolism), Xbp1 (cyclin implicated in the regulation of carbohydrate and amino acid metabolism), and Hfi1 (involved in the formation of the SAGA complex). These results evidence the crucial role of histone lysine acetylation levels in the regulation of gene expression in the YMC through the coordinated action of transcription factors and lysine acetyltransferases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The Yeast Metabolic Cycle (YMC) is a model system in which levels of around 60% of the yeast transcripts cycle over time. The spatial and temporal resolution provided by the YMC has revealed that changes in the yeast metabolic landscape and chromatin status can be related to cycling gene expression. However, the interplay between histone modifications and transcription factor activity during the YMC is still poorly understood. Here we apply an innovative statistical approach to integrate chromatin state (ChIP-seq) and gene expression (RNA-seq) data to investigate the transcriptional control during the YMC. By using the multivariate regression models N-PLS (Partial Least Squares) and MORE (Multi-Omics REgulation) methodologies, we assessed the contribution of histone marks and transcription factors to the regulation of gene expression in the YMC. We found that H3K18ac and H3K9ac were the most important histone modifications, whereas Sfp1, Hfi1, Pip2, Mig2, and Yhp1 emerged as the most relevant transcription factors. A significant association in the co-regulation of gene expression was found between H3K18ac and the transcription factors Pip2 (involved in fatty acids metabolism), Xbp1 (cyclin implicated in the regulation of carbohydrate and amino acid metabolism), and Hfi1 (involved in the formation of the SAGA complex). These results evidence the crucial role of histone lysine acetylation levels in the regulation of gene expression in the YMC through the coordinated action of transcription factors and lysine acetyltransferases.
108.
Arroyo-Crespo, Juan J.; Armiñán, Ana; Charbonnier, David; Balzano-Nogueira, Leandro; Huertas-López, Francisco; Martí, Cristina; Tarazona, Sonia; Forteza, Jerónimo; Conesa, Ana; Vicent, María J.
Tumor microenvironment-targeted poly-L-glutamic acid-based combination conjugate for enhanced triple negative breast cancer treatment Journal Article
In: Biomaterials, vol. 186, pp. 8 - 21, 2018, ISSN: 0142-9612.
@article{ARROYOCRESPO20188,
title = {Tumor microenvironment-targeted poly-L-glutamic acid-based combination conjugate for enhanced triple negative breast cancer treatment},
author = {Juan J. Arroyo-Crespo and Ana Armiñán and David Charbonnier and Leandro Balzano-Nogueira and Francisco Huertas-López and Cristina Martí and Sonia Tarazona and Jerónimo Forteza and Ana Conesa and María J. Vicent},
url = {http://www.sciencedirect.com/science/article/pii/S0142961218306604},
doi = {https://doi.org/10.1016/j.biomaterials.2018.09.023},
issn = {0142-9612},
year = {2018},
date = {2018-09-18},
journal = {Biomaterials},
volume = {186},
pages = {8 - 21},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
107.
Colli-Dula, Reyna Cristina; Fang, Xiefan; Moraga-Amador, David; Albornoz-Abud, Nacira; Zamora-Bustillos, Roberto; Conesa, Ana; Zapata-Perez, Omar; Moreno, Diego; Hernandez-Nuñez, Emanuel
Gene expression profile and molecular pathway datasets resulting from benzo(a)pyrene exposure in the liver and testis of adult tilapia Journal Article
In: Data in Brief, vol. 20, pp. 1500 - 1509, 2018, ISSN: 2352-3409.
@article{COLLIDULA20181500,
title = {Gene expression profile and molecular pathway datasets resulting from benzo(a)pyrene exposure in the liver and testis of adult tilapia},
author = {Reyna Cristina Colli-Dula and Xiefan Fang and David Moraga-Amador and Nacira Albornoz-Abud and Roberto Zamora-Bustillos and Ana Conesa and Omar Zapata-Perez and Diego Moreno and Emanuel Hernandez-Nuñez},
url = {http://www.sciencedirect.com/science/article/pii/S2352340918310667},
doi = {https://doi.org/10.1016/j.dib.2018.08.206},
issn = {2352-3409},
year = {2018},
date = {2018-09-05},
journal = {Data in Brief},
volume = {20},
pages = {1500 - 1509},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
106.
Newman, Jeremy R. B.; Concannon, Patrick; Tardaguila, Manuel; Conesa, Ana; McIntyre, Lauren M.
Event Analysis: Using Transcript Events To Improve Estimates of Abundance in RNA-seq Data Journal Article
In: G3: Genes, Genomes, Genetics, vol. 8, no. 9, pp. 2923–2940, 2018.
@article{Newman2923,
title = {Event Analysis: Using Transcript Events To Improve Estimates of Abundance in RNA-seq Data},
author = { Jeremy R. B. Newman and Patrick Concannon and Manuel Tardaguila and Ana Conesa and Lauren M. McIntyre},
url = {http://www.g3journal.org/content/8/9/2923},
doi = {10.1534/g3.118.200373},
year = {2018},
date = {2018-08-30},
journal = {G3: Genes, Genomes, Genetics},
volume = {8},
number = {9},
pages = {2923--2940},
publisher = {G3: Genes, Genomes, Genetics},
abstract = {Alternative splicing leverages genomic content by allowing the synthesis of multiple transcripts and, by implication, protein isoforms, from a single gene. However, estimating the abundance of transcripts produced in a given tissue from short sequencing reads is difficult and can result in both the construction of transcripts that do not exist, and the failure to identify true transcripts. An alternative approach is to catalog the events that make up isoforms (splice junctions and exons). We present here the Event Analysis (EA) approach, where we project transcripts onto the genome and identify overlapping/unique regions and junctions. In addition, all possible logical junctions are assembled into a catalog. Transcripts are filtered before quantitation based on simple measures: the proportion of the events detected, and the coverage. We find that mapping to a junction catalog is more efficient at detecting novel junctions than mapping in a splice aware manner. We identify 99.8% of true transcripts while iReckon identifies 82% of the true transcripts and creates more transcripts not included in the simulation than were initially used in the simulation. Using PacBio Iso-seq data from a mouse neural progenitor cell model, EA detects 60% of the novel junctions that are combinations of existing exons while only 43% are detected by STAR. EA further detects ~5,000 annotated junctions missed by STAR. Filtering transcripts based on the proportion of the transcript detected and the number of reads on average supporting that transcript captures 95% of the PacBio transcriptome. Filtering the reference transcriptome before quantitation, results in is a more stable estimate of isoform abundance, with improved correlation between replicates. This was particularly evident when EA is applied to an RNA-seq study of type 1 diabetes (T1D), where the coefficient of variation among subjects (n = 81) in the transcript abundance estimates was substantially reduced compared to the estimation using the full reference. EA focuses on individual transcriptional events. These events can be quantitate and analyzed directly or used to identify the probable set of expressed transcripts. Simple rules based on detected events and coverage used in filtering result in a dramatic improvement in isoform estimation without the use of ancillary data (e.g., ChIP, long reads) that may not be available for many studies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alternative splicing leverages genomic content by allowing the synthesis of multiple transcripts and, by implication, protein isoforms, from a single gene. However, estimating the abundance of transcripts produced in a given tissue from short sequencing reads is difficult and can result in both the construction of transcripts that do not exist, and the failure to identify true transcripts. An alternative approach is to catalog the events that make up isoforms (splice junctions and exons). We present here the Event Analysis (EA) approach, where we project transcripts onto the genome and identify overlapping/unique regions and junctions. In addition, all possible logical junctions are assembled into a catalog. Transcripts are filtered before quantitation based on simple measures: the proportion of the events detected, and the coverage. We find that mapping to a junction catalog is more efficient at detecting novel junctions than mapping in a splice aware manner. We identify 99.8% of true transcripts while iReckon identifies 82% of the true transcripts and creates more transcripts not included in the simulation than were initially used in the simulation. Using PacBio Iso-seq data from a mouse neural progenitor cell model, EA detects 60% of the novel junctions that are combinations of existing exons while only 43% are detected by STAR. EA further detects ~5,000 annotated junctions missed by STAR. Filtering transcripts based on the proportion of the transcript detected and the number of reads on average supporting that transcript captures 95% of the PacBio transcriptome. Filtering the reference transcriptome before quantitation, results in is a more stable estimate of isoform abundance, with improved correlation between replicates. This was particularly evident when EA is applied to an RNA-seq study of type 1 diabetes (T1D), where the coefficient of variation among subjects (n = 81) in the transcript abundance estimates was substantially reduced compared to the estimation using the full reference. EA focuses on individual transcriptional events. These events can be quantitate and analyzed directly or used to identify the probable set of expressed transcripts. Simple rules based on detected events and coverage used in filtering result in a dramatic improvement in isoform estimation without the use of ancillary data (e.g., ChIP, long reads) that may not be available for many studies.
105.
Arzalluz-Luque, Ángeles; Ana, Conesa
Single-cell RNAseq for the study of isoforms---how is that possible? Journal Article
In: Genome Biology, vol. 19, no. 1, pp. 110, 2018, ISSN: 1474-760X.
@article{Arzalluz-Luque2018,
title = {Single-cell RNAseq for the study of isoforms---how is that possible?},
author = {Ángeles Arzalluz-Luque and Conesa Ana },
url = {http://doi.org/10.1186/s13059-018-1496-z},
doi = {10.1186/s13059-018-1496-z},
issn = {1474-760X},
year = {2018},
date = {2018-08-10},
journal = {Genome Biology},
volume = {19},
number = {1},
pages = {110},
abstract = {Single-cell RNAseq and alternative splicing studies have recently become two of the most prominent applications of RNAseq. However, the combination of both is still challenging, and few research efforts have been dedicated to the intersection between them. Cell-level insight on isoform expression is required to fully understand the biology of alternative splicing, but it is still an open question to what extent isoform expression analysis at the single-cell level is actually feasible. Here, we establish a set of four conditions that are required for a successful single-cell-level isoform study and evaluate how these conditions are met by these technologies in published research.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Single-cell RNAseq and alternative splicing studies have recently become two of the most prominent applications of RNAseq. However, the combination of both is still challenging, and few research efforts have been dedicated to the intersection between them. Cell-level insight on isoform expression is required to fully understand the biology of alternative splicing, but it is still an open question to what extent isoform expression analysis at the single-cell level is actually feasible. Here, we establish a set of four conditions that are required for a successful single-cell-level isoform study and evaluate how these conditions are met by these technologies in published research.
104.
Colli-Dula, Reyna Cristina; Fang, Xiefan; Moraga-Amador, David; Albornoz-Abud, Nacira; Zamora-Bustillos, Roberto; Conesa, Ana; Zapata-Perez, Omar; Moreno, Diego; Hernandez-Nuñez, Emanuel
Transcriptome analysis reveals novel insights into the response of low-dose benzo(a)pyrene exposure in male tilapia Journal Article
In: Aquatic Toxicology, vol. 201, pp. 162 - 173, 2018, ISSN: 0166-445X.
@article{Colli-Dula2018,
title = {Transcriptome analysis reveals novel insights into the response of low-dose benzo(a)pyrene exposure in male tilapia},
author = {Reyna Cristina Colli-Dula and Xiefan Fang and David Moraga-Amador and Nacira Albornoz-Abud and Roberto Zamora-Bustillos and Ana Conesa and Omar Zapata-Perez and Diego Moreno and Emanuel Hernandez-Nuñez},
url = {http://www.sciencedirect.com/science/article/pii/S0166445X18303503},
doi = {10.1016/j.aquatox.2018.06.005},
issn = {0166-445X},
year = {2018},
date = {2018-08-01},
journal = {Aquatic Toxicology},
volume = {201},
pages = {162 - 173},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
103.
Tarazona, Sonia; Balzano-Nogueira, Leandro; Conesa, Ana
Multiomics Data Integration in Time Series Experiments Journal Article
In: Comprehensive Analytical Chemistry, vol. 8, pp. 505-532, 2018.
@article{tarazona2018multiomics,
title = {Multiomics Data Integration in Time Series Experiments},
author = { Sonia Tarazona and Leandro Balzano-Nogueira and Ana Conesa},
url = {https://doi.org/10.1016/bs.coac.2018.06.005},
doi = {10.1016/bs.coac.2018.06.005},
year = {2018},
date = {2018-07-31},
journal = {Comprehensive Analytical Chemistry},
volume = {8},
pages = {505-532},
publisher = {Elsevier},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
102.
Hernández-de-Diego, Rafael; Tarazona, Sonia; Martínez-Mira, Carlos; Balzano-Nogueira, Leandro; Furió-Tarí, Pedro; Jr Pappas, Georgios J; Conesa, Ana
PaintOmics 3: a web resource for the pathway analysis and visualization of multi-omics data Journal Article
In: Nucleic Acids Research, pp. gky466, 2018.
@article{Hernández-de-Diego2018,
title = {PaintOmics 3: a web resource for the pathway analysis and visualization of multi-omics data},
author = {Hernández-de-Diego, Rafael and Tarazona, Sonia and Martínez-Mira, Carlos and Balzano-Nogueira, Leandro and Furió-Tarí, Pedro and Pappas, Jr ,Georgios J and Conesa, Ana},
url = {http://dx.doi.org/10.1093/nar/gky466},
doi = {http://dx.doi.org/10.1093/nar/gky466},
year = {2018},
date = {2018-07-02},
journal = {Nucleic Acids Research},
pages = {gky466},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
101.
Babilonia, Joany; Conesa, Ana; Casaburi, Giorgio; Pereira, Cecile; Louyakis, Artemis S.; Reid, R. Pamela; Foster, Jamie S.
Comparative Metagenomics Provides Insight Into the Ecosystem Functioning of the Shark Bay Stromatolites, Western Australia Journal Article
In: Frontiers in Microbiology, vol. 9, pp. 1359, 2018, ISSN: 1664-302X.
@article{10.3389/fmicb.2018.01359,
title = {Comparative Metagenomics Provides Insight Into the Ecosystem Functioning of the Shark Bay Stromatolites, Western Australia},
author = {Joany Babilonia and Ana Conesa and Giorgio Casaburi and Cecile Pereira and Artemis S. Louyakis and R. Pamela Reid and Jamie S. Foster},
url = {http://www.frontiersin.org/article/10.3389/fmicb.2018.01359},
doi = {10.3389/fmicb.2018.01359},
issn = {1664-302X},
year = {2018},
date = {2018-06-25},
journal = {Frontiers in Microbiology},
volume = {9},
pages = {1359},
abstract = {Stromatolites are organosedimentary build-ups that have formed as a result of the sediment trapping, binding and precipitating activities of microbes. Today, extant systems provide an ideal platform for understanding the structure, composition, and interactions between stromatolite-forming microbial communities and their respective environments. In this study, we compared the metagenomes of three prevalent stromatolite-forming microbial mat types in the Spaven Province of Hamelin Pool, Shark Bay located in Western Australia. These stromatolite-forming mat types included an intertidal pustular mat as well as a smooth and colloform mat types located in the subtidal zone. Additionally, the metagenomes of an adjacent, non-lithifying mat located in the upper intertidal zone were also sequenced for comparative purposes. Taxonomic and functional gene analyses revealed distinctive differences between the lithifying and non-lithifying mat types, which strongly correlated with water depth. Three distinct populations emerged including the upper intertidal non-lithifying mats, the intertidal pustular mats associated with unlaminated carbonate build-ups, and the subtidal colloform and smooth mat types associated with laminated structures. Functional analysis of metagenomes revealed that amongst stromatolite-forming mats there was an enrichment of photosynthesis pathways in the pustular stromatolite-forming mats. In the colloform and smooth stromatolite-forming mats, however, there was an increase in the abundance of genes associated with those heterotrophic metabolisms typically associated with carbonate mineralization, such as sulfate reduction. The comparative metagenomic analyses suggest that stromatolites of Hamelin Pool may form by two distinctive processes that are highly dependent on water depth. These results provide key insight into the potential adaptive strategies and synergistic interactions between microbes and their environments that may lead to stromatolite formation and accretion.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Stromatolites are organosedimentary build-ups that have formed as a result of the sediment trapping, binding and precipitating activities of microbes. Today, extant systems provide an ideal platform for understanding the structure, composition, and interactions between stromatolite-forming microbial communities and their respective environments. In this study, we compared the metagenomes of three prevalent stromatolite-forming microbial mat types in the Spaven Province of Hamelin Pool, Shark Bay located in Western Australia. These stromatolite-forming mat types included an intertidal pustular mat as well as a smooth and colloform mat types located in the subtidal zone. Additionally, the metagenomes of an adjacent, non-lithifying mat located in the upper intertidal zone were also sequenced for comparative purposes. Taxonomic and functional gene analyses revealed distinctive differences between the lithifying and non-lithifying mat types, which strongly correlated with water depth. Three distinct populations emerged including the upper intertidal non-lithifying mats, the intertidal pustular mats associated with unlaminated carbonate build-ups, and the subtidal colloform and smooth mat types associated with laminated structures. Functional analysis of metagenomes revealed that amongst stromatolite-forming mats there was an enrichment of photosynthesis pathways in the pustular stromatolite-forming mats. In the colloform and smooth stromatolite-forming mats, however, there was an increase in the abundance of genes associated with those heterotrophic metabolisms typically associated with carbonate mineralization, such as sulfate reduction. The comparative metagenomic analyses suggest that stromatolites of Hamelin Pool may form by two distinctive processes that are highly dependent on water depth. These results provide key insight into the potential adaptive strategies and synergistic interactions between microbes and their environments that may lead to stromatolite formation and accretion.
100.
Delaye, Luis; Ruiz-Ruiz, Susana; Calderon, Enrique; Tarazona, Sonia; Conesa, Ana; Moya, Andrés
Evidence of the Red-Queen Hypothesis from Accelerated Rates of Evolution of Genes Involved in Biotic Interactions in Pneumocystis Journal Article
In: Genome Biology and Evolution, vol. 10, no. 6, pp. 1596-1606, 2018.
@article{doi:10.1093/gbe/evy116,
title = {Evidence of the Red-Queen Hypothesis from Accelerated Rates of Evolution of Genes Involved in Biotic Interactions in Pneumocystis},
author = { Luis Delaye and Susana Ruiz-Ruiz and Enrique Calderon and Sonia Tarazona and Ana Conesa and Andrés Moya},
url = {http://dx.doi.org/10.1093/gbe/evy116},
doi = {10.1093/gbe/evy116},
year = {2018},
date = {2018-06-01},
journal = {Genome Biology and Evolution},
volume = {10},
number = {6},
pages = {1596-1606},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
99.
Zhu, Qile; Li, Xiaolin; Conesa, Ana; Pereira, Cécile
GRAM-CNN: a deep learning approach with local context for named entity recognition in biomedical text Journal Article
In: Bioinformatics, vol. 34, no. 9, pp. 1547-1554, 2018.
@article{Zhu2018,
title = {GRAM-CNN: a deep learning approach with local context for named entity recognition in biomedical text},
author = {Zhu, Qile and Li, Xiaolin and Conesa, Ana and Pereira, Cécile},
url = {http://dx.doi.org/10.1093/bioinformatics/btx815},
doi = {10.1093/bioinformatics/btx815},
year = {2018},
date = {2018-05-01},
journal = {Bioinformatics},
volume = {34},
number = {9},
pages = {1547-1554},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
98.
García-Molinero, Varinia; Garcíaa-Martínez, José; Reja, Rohit; Furió-Tarí, Pedro; Antúnez, Oreto; Vinayachandran, Vinesh; Conesa, Ana; Pugh, B. Franklin; Pérez-Ortín, José E.; Rodríguez-Navarro, Susana
The SAGA/TREX-2 subunit Sus1 binds widely to transcribed genes and affects mRNA turnover globally Journal Article
In: Epigenetics & Chromatin, vol. 11, no. 1, pp. 13, 2018.
@article{García-Molinero2018,
title = {The SAGA/TREX-2 subunit Sus1 binds widely to transcribed genes and affects mRNA turnover globally},
author = {García-Molinero, Varinia and Garcíaa-Martínez, José and Reja, Rohit and Furió-Tarí, Pedro and Antúnez, Oreto and Vinayachandran, Vinesh and Conesa, Ana and Pugh, B. Franklin and Pérez-Ortín, José E. and Rodríguez-Navarro, Susana},
url = {http://doi.org/10.1186/s13072-018-0184-2},
doi = {10.1186/s13072-018-0184-2},
year = {2018},
date = {2018-03-29},
journal = {Epigenetics & Chromatin},
volume = {11},
number = {1},
pages = {13},
abstract = {Eukaryotic transcription is regulated through two complexes, the general transcription factor IID (TFIID) and the coactivator Spt--Ada--Gcn5 acetyltransferase (SAGA). Recent findings confirm that both TFIID and SAGA contribute to the synthesis of nearly all transcripts and are recruited genome-wide in yeast. However, how this broad recruitment confers selectivity under specific conditions remains an open question.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Eukaryotic transcription is regulated through two complexes, the general transcription factor IID (TFIID) and the coactivator Spt--Ada--Gcn5 acetyltransferase (SAGA). Recent findings confirm that both TFIID and SAGA contribute to the synthesis of nearly all transcripts and are recruited genome-wide in yeast. However, how this broad recruitment confers selectivity under specific conditions remains an open question.
97.
Tardaguila, Manuel; de la Fuente, Lorena; Marti, Cristina; Pereira, Cécile; Pardo-Palacios, Francisco Jose; del Risco, Hector; Ferrell, Marc; Mellado, Maravillas; Macchietto, Marissa; Verheggen, Kenneth; Edelmann, Mariola; Ezkurdia, Iakes; Vazquez, Jesus; Tress, Michael; Mortazavi, Ali; Martens, Lennart; Rodriguez-Navarro, Susana; Moreno-Manzano, Victoria; Conesa, Ana
In: Genome Research, 2018.
@article{Tardaguila2018,
title = {SQANTI: extensive characterization of long-read transcript sequences for quality control in full-length transcriptome identification and quantification},
author = {Tardaguila, Manuel and de la Fuente, Lorena and Marti, Cristina and Pereira, Cécile and Pardo-Palacios, Francisco Jose and del Risco, Hector and Ferrell, Marc and Mellado, Maravillas and Macchietto, Marissa and Verheggen, Kenneth and Edelmann, Mariola and Ezkurdia, Iakes and Vazquez, Jesus and Tress, Michael and Mortazavi, Ali and Martens, Lennart and Rodriguez-Navarro, Susana and Moreno-Manzano, Victoria and Conesa, Ana},
url = {http://genome.cshlp.org/content/early/2018/02/09/gr.222976.117.abstract},
doi = {10.1101/gr.222976.117},
year = {2018},
date = {2018-02-09},
journal = {Genome Research},
abstract = {High-throughput sequencing of full-length transcripts using long reads has paved the way for the discovery of thousands of novel transcripts, even in well-annotated mammalian species. The advances in sequencing technology have created a need for studies and tools that can characterize these novel variants. Here, we present SQANTI, an automated pipeline for the classification of long-read transcripts that can assess the quality of data and the preprocessing pipeline using 47 unique descriptors. We apply SQANTI to a neuronal mouse transcriptome using Pacific Biosciences (PacBio) long reads and illustrate how the tool is effective in characterizing and describing the composition of the full-length transcriptome. We perform extensive evaluation of ToFU PacBio transcripts by PCR to reveal that an important number of the novel transcripts are technical artifacts of the sequencing approach and that SQANTI quality descriptors can be used to engineer a filtering strategy to remove them. Most novel transcripts in this curated transcriptome are novel combinations of existing splice sites, resulting more frequently in novel ORFs than novel UTRs, and are enriched in both general metabolic and neural-specific functions. We show that these new transcripts have a major impact in the correct quantification of transcript levels by state-of-the-art short-read-based quantification algorithms. By comparing our iso-transcriptome with public proteomics databases, we find that alternative isoforms are elusive to proteogenomics detection. SQANTI allows the user to maximize the analytical outcome of long-read technologies by providing the tools to deliver quality-evaluated and curated full-length transcriptomes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
High-throughput sequencing of full-length transcripts using long reads has paved the way for the discovery of thousands of novel transcripts, even in well-annotated mammalian species. The advances in sequencing technology have created a need for studies and tools that can characterize these novel variants. Here, we present SQANTI, an automated pipeline for the classification of long-read transcripts that can assess the quality of data and the preprocessing pipeline using 47 unique descriptors. We apply SQANTI to a neuronal mouse transcriptome using Pacific Biosciences (PacBio) long reads and illustrate how the tool is effective in characterizing and describing the composition of the full-length transcriptome. We perform extensive evaluation of ToFU PacBio transcripts by PCR to reveal that an important number of the novel transcripts are technical artifacts of the sequencing approach and that SQANTI quality descriptors can be used to engineer a filtering strategy to remove them. Most novel transcripts in this curated transcriptome are novel combinations of existing splice sites, resulting more frequently in novel ORFs than novel UTRs, and are enriched in both general metabolic and neural-specific functions. We show that these new transcripts have a major impact in the correct quantification of transcript levels by state-of-the-art short-read-based quantification algorithms. By comparing our iso-transcriptome with public proteomics databases, we find that alternative isoforms are elusive to proteogenomics detection. SQANTI allows the user to maximize the analytical outcome of long-read technologies by providing the tools to deliver quality-evaluated and curated full-length transcriptomes.
96.
Nueda, María José; Martorell-Marugan, Jordi; Martí, Cristina; Tarazona, Sonia; Conesa, Ana
Identification and visualization of differential isoform expression in RNA-seq time series Journal Article
In: Bioinformatics, vol. 34, no. 3, pp. 524-526, 2018.
@article{doi:10.1093/bioinformatics/btx578,
title = {Identification and visualization of differential isoform expression in RNA-seq time series},
author = { María José Nueda and Jordi Martorell-Marugan and Cristina Martí and Sonia Tarazona and Ana Conesa},
url = {http://dx.doi.org/10.1093/bioinformatics/btx578},
doi = {10.1093/bioinformatics/btx578},
year = {2018},
date = {2018-02-01},
journal = {Bioinformatics},
volume = {34},
number = {3},
pages = {524-526},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
95.
Martínez-Mira, Carlos; Conesa, Ana; Tarazona, Sonia
MOSim: Multi-Omics Simulation in R Journal Article Forthcoming
In: bioRxiv, pp. 421834, Forthcoming.
@article{martinez2018mosim,
title = {MOSim: Multi-Omics Simulation in R},
author = { Carlos Martínez-Mira and Ana Conesa and Sonia Tarazona},
url = {https://doi.org/10.1101/421834},
doi = {10.1101/421834},
year = {2018},
date = {2018-01-01},
journal = {bioRxiv},
pages = {421834},
publisher = {Cold Spring Harbor Laboratory},
keywords = {},
pubstate = {forthcoming},
tppubtype = {article}
}
2017
94.
Kaeding, N.; Kaufhold, I.; Mueller, C.; Szaszak, M.; Shima, K.; Weinmaier, T.; Lomas, R.; Conesa, A.; Schmitt-Kopplin, P.; Rattei, T.; Rupp, J.
Growth of Chlamydia pneumoniae Is Enhanced in Cell swith Impaired Mitochondrial Function Journal Article
In: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, vol. 7, 2017, ISSN: 2235-2988.
@article{ISI:000417056500003,
title = {Growth of Chlamydia pneumoniae Is Enhanced in Cell swith Impaired
Mitochondrial Function},
author = { N. Kaeding and I. Kaufhold and C. Mueller and M. Szaszak and K. Shima and T. Weinmaier and R. Lomas and A. Conesa and P. Schmitt-Kopplin and T. Rattei and J. Rupp},
url = {http://dx.doi.org/10.3389/fcimb.2017.00499},
doi = {10.3389/fcimb.2017.00499},
issn = {2235-2988},
year = {2017},
date = {2017-12-01},
journal = {FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY},
volume = {7},
abstract = {Effective growth and replication of obligate intracellular pathogens
depend on host cell metabolism. How this is connected to host cell
mitochondrial function has not been studied so far. Recent studies
suggest that growth of intracellular bacteria such as Chlamydia
pneumoniae is enhanced in a low oxygen environment, arguing for a
particular mechanistic role of the mitochondrial respiration in
controlling intracellular progeny. Metabolic changes in C. pneumoniae
infected epithelial cells were analyzed under normoxic (O-2 approximate
to 20%) and hypoxic conditions (O-2 < 3%). We observed that infection
of epithelial cells with C. pneumoniae under normoxia impaired
mitochondrial function characterized by an enhanced mitochondrial
membrane potential and ROS generation. Knockdown and mutation of the
host cell ATP synthase resulted in an increased chlamydial replication
already under normoxic conditions. As expected, mitochondrial
hyperpolarization was observed in non-infected control cells cultured
under hypoxic conditions, which was beneficial for C. pneumoniae growth.
Taken together, functional and genetically encoded mitochondrial
dysfunction strongly promotes intracellular growth of C. pneumoniae.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Effective growth and replication of obligate intracellular pathogens
depend on host cell metabolism. How this is connected to host cell
mitochondrial function has not been studied so far. Recent studies
suggest that growth of intracellular bacteria such as Chlamydia
pneumoniae is enhanced in a low oxygen environment, arguing for a
particular mechanistic role of the mitochondrial respiration in
controlling intracellular progeny. Metabolic changes in C. pneumoniae
infected epithelial cells were analyzed under normoxic (O-2 approximate
to 20%) and hypoxic conditions (O-2 < 3%). We observed that infection
of epithelial cells with C. pneumoniae under normoxia impaired
mitochondrial function characterized by an enhanced mitochondrial
membrane potential and ROS generation. Knockdown and mutation of the
host cell ATP synthase resulted in an increased chlamydial replication
already under normoxic conditions. As expected, mitochondrial
hyperpolarization was observed in non-infected control cells cultured
under hypoxic conditions, which was beneficial for C. pneumoniae growth.
Taken together, functional and genetically encoded mitochondrial
dysfunction strongly promotes intracellular growth of C. pneumoniae.
depend on host cell metabolism. How this is connected to host cell
mitochondrial function has not been studied so far. Recent studies
suggest that growth of intracellular bacteria such as Chlamydia
pneumoniae is enhanced in a low oxygen environment, arguing for a
particular mechanistic role of the mitochondrial respiration in
controlling intracellular progeny. Metabolic changes in C. pneumoniae
infected epithelial cells were analyzed under normoxic (O-2 approximate
to 20%) and hypoxic conditions (O-2 < 3%). We observed that infection
of epithelial cells with C. pneumoniae under normoxia impaired
mitochondrial function characterized by an enhanced mitochondrial
membrane potential and ROS generation. Knockdown and mutation of the
host cell ATP synthase resulted in an increased chlamydial replication
already under normoxic conditions. As expected, mitochondrial
hyperpolarization was observed in non-infected control cells cultured
under hypoxic conditions, which was beneficial for C. pneumoniae growth.
Taken together, functional and genetically encoded mitochondrial
dysfunction strongly promotes intracellular growth of C. pneumoniae.
93.
Newman, J. R. B.; Conesa, A.; Mika, M.; New, F. N.; Onengut-Gumuscu, S.; Atkinson, M. A.; Rich, S. S.; McIntyre, L. M.; Concannon, P.
In: GENOME RESEARCH, vol. 27, no. 11, pp. 1807-1815, 2017, ISSN: 1088-9051.
@article{ISI:000414165900003,
title = {Disease-specific biases in alternative splicing and tissue-specific
dysregulation revealed by multitissue profiling of lymphocyte gene
expression in type 1 diabetes},
author = { J. R. B. Newman and A. Conesa and M. Mika and F. N. New and S. Onengut-Gumuscu and M. A. Atkinson and S. S. Rich and L. M. McIntyre and P. Concannon},
url = {http://dx.doi.org/10.1101/gr.217984.116},
doi = {10.1101/gr.217984.116},
issn = {1088-9051},
year = {2017},
date = {2017-11-01},
journal = {GENOME RESEARCH},
volume = {27},
number = {11},
pages = {1807-1815},
abstract = {Genome-wide association studies (GWAS) have identified multiple, shared
allelic associations with many autoimmune diseases. However, the
pathogenic contributions of variants residing in risk loci remain
unresolved. The location of the majority of shared disease-associated
variants in noncoding regions suggests they contribute to risk of
autoimmunity through effects on gene expression in the immune system. In
the current study, we test this hypothesis by applying RNA sequencing to
CD4(+), CD8(+), and CD19(+) lymphocyte populations isolated from 81
subjects with type 1 diabetes (T1D). We characterize and compare the
expression patterns across these cell types for three gene sets: all
genes, the set of genes implicated in autoimmune disease risk by GWAS, and the subset of these genes specifically implicated in T1D. We
performed RNA sequencing and aligned the reads to both the human
reference genome and a catalog of all possible splicing events developed
from the genome, thereby providing a comprehensive evaluation of the
roles of gene expression and alternative splicing (AS) in autoimmunity.
Autoimmune candidate genes displayed greater expression specificity in
the three lymphocyte populations relative to other genes, with
significantly increased levels of splicing events, particularly those
predicted to have substantial effects on protein isoform structure and
function (e.g., intron retention, exon skipping). The majority of
single-nucleotide polymorphisms within T1D-associated loci were also
associated with one or more cis-expression quantitative trait loci
(ciseQTLs) and/or splicing eQTLs. Our findings highlight a substantial, and previously underrecognized, role for AS in the pathogenesis of
autoimmune disorders and particularly for T1D.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Genome-wide association studies (GWAS) have identified multiple, shared
allelic associations with many autoimmune diseases. However, the
pathogenic contributions of variants residing in risk loci remain
unresolved. The location of the majority of shared disease-associated
variants in noncoding regions suggests they contribute to risk of
autoimmunity through effects on gene expression in the immune system. In
the current study, we test this hypothesis by applying RNA sequencing to
CD4(+), CD8(+), and CD19(+) lymphocyte populations isolated from 81
subjects with type 1 diabetes (T1D). We characterize and compare the
expression patterns across these cell types for three gene sets: all
genes, the set of genes implicated in autoimmune disease risk by GWAS, and the subset of these genes specifically implicated in T1D. We
performed RNA sequencing and aligned the reads to both the human
reference genome and a catalog of all possible splicing events developed
from the genome, thereby providing a comprehensive evaluation of the
roles of gene expression and alternative splicing (AS) in autoimmunity.
Autoimmune candidate genes displayed greater expression specificity in
the three lymphocyte populations relative to other genes, with
significantly increased levels of splicing events, particularly those
predicted to have substantial effects on protein isoform structure and
function (e.g., intron retention, exon skipping). The majority of
single-nucleotide polymorphisms within T1D-associated loci were also
associated with one or more cis-expression quantitative trait loci
(ciseQTLs) and/or splicing eQTLs. Our findings highlight a substantial, and previously underrecognized, role for AS in the pathogenesis of
autoimmune disorders and particularly for T1D.
allelic associations with many autoimmune diseases. However, the
pathogenic contributions of variants residing in risk loci remain
unresolved. The location of the majority of shared disease-associated
variants in noncoding regions suggests they contribute to risk of
autoimmunity through effects on gene expression in the immune system. In
the current study, we test this hypothesis by applying RNA sequencing to
CD4(+), CD8(+), and CD19(+) lymphocyte populations isolated from 81
subjects with type 1 diabetes (T1D). We characterize and compare the
expression patterns across these cell types for three gene sets: all
genes, the set of genes implicated in autoimmune disease risk by GWAS, and the subset of these genes specifically implicated in T1D. We
performed RNA sequencing and aligned the reads to both the human
reference genome and a catalog of all possible splicing events developed
from the genome, thereby providing a comprehensive evaluation of the
roles of gene expression and alternative splicing (AS) in autoimmunity.
Autoimmune candidate genes displayed greater expression specificity in
the three lymphocyte populations relative to other genes, with
significantly increased levels of splicing events, particularly those
predicted to have substantial effects on protein isoform structure and
function (e.g., intron retention, exon skipping). The majority of
single-nucleotide polymorphisms within T1D-associated loci were also
associated with one or more cis-expression quantitative trait loci
(ciseQTLs) and/or splicing eQTLs. Our findings highlight a substantial, and previously underrecognized, role for AS in the pathogenesis of
autoimmune disorders and particularly for T1D.
92.
Merino, Gabriela A.; Conesa, Ana; Fernández, Elmer A.
A benchmarking of workflows for detecting differential splicing and differential expression at isoform level in human RNA-seq studies Journal Article
In: Briefings in Bioinformatics, pp. bbx122, 2017.
@article{doi:10.1093/bib/bbx122,
title = {A benchmarking of workflows for detecting differential splicing and differential expression at isoform level in human RNA-seq studies},
author = { Gabriela A. Merino and Ana Conesa and Elmer A. Fernández},
url = {http://dx.doi.org/10.1093/bib/bbx122},
doi = {10.1093/bib/bbx122},
year = {2017},
date = {2017-10-13},
journal = {Briefings in Bioinformatics},
pages = {bbx122},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
91.
Conesa, A.; Fernandez, M.; Exposito, R.; Campos, J.; Lamua, J. Ramon; del Pilar Navarro, M.; Rubio-Munoz, P.; Ahijado-Guzman, P.; Gonzalez, C. M.
Certolizumab Pegol Effectiveness and Retention Rate in Psoriatic Arthritis. Real Life Data Journal Article
In: ARTHRITIS & RHEUMATOLOGY, vol. 69, no. 10, 2017, ISSN: 2326-5191.
@article{ISI:000411824103042,
title = {Certolizumab Pegol Effectiveness and Retention Rate in Psoriatic
Arthritis. Real Life Data},
author = { A. Conesa and M. Fernandez and R. Exposito and J. Campos and J. Ramon Lamua and M. del Pilar Navarro and P. Rubio-Munoz and P. Ahijado-Guzman and C. M. Gonzalez},
issn = {2326-5191},
year = {2017},
date = {2017-10-01},
journal = {ARTHRITIS & RHEUMATOLOGY},
volume = {69},
number = {10},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
90.
Gomez-Cabrero, D.; Marabita, F.; Tarazona, S.; Cano, I.; Roca, J.; Conesa, A.; Sabatier, P.; Tegner, J.
Guidelines for Developing Successful Short Advanced Courses in Systems Medicine and Systems Biology Journal Article
In: CELL SYSTEMS, vol. 5, no. 3, pp. 168-175, 2017, ISSN: 2405-4712.
@article{ISI:000411874500006,
title = {Guidelines for Developing Successful Short Advanced Courses in Systems
Medicine and Systems Biology},
author = { D. Gomez-Cabrero and F. Marabita and S. Tarazona and I. Cano and J. Roca and A. Conesa and P. Sabatier and J. Tegner},
url = {http://dx.doi.org/10.1016/j.cels.2017.05.013},
doi = {10.1016/j.cels.2017.05.013},
issn = {2405-4712},
year = {2017},
date = {2017-09-01},
journal = {CELL SYSTEMS},
volume = {5},
number = {3},
pages = {168-175},
abstract = {Systems medicine and systems biology have inherent educational
challenges. These have largely been addressed either by providing new
masters programs or by redesigning undergraduate programs. In contrast, short courses can respond to a different need: they can provide
condensed updates for professionals across academia, the clinic, and
industry. These courses have received less attention. Here, we share our
experiences in developing and providing such courses to current and
future leaders in systems biology and systems medicine. We present
guidelines for how to reproduce our courses, and we offer suggestions
for how to select students who will nurture an interdisciplinary
learning environment and thrive there.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Systems medicine and systems biology have inherent educational
challenges. These have largely been addressed either by providing new
masters programs or by redesigning undergraduate programs. In contrast, short courses can respond to a different need: they can provide
condensed updates for professionals across academia, the clinic, and
industry. These courses have received less attention. Here, we share our
experiences in developing and providing such courses to current and
future leaders in systems biology and systems medicine. We present
guidelines for how to reproduce our courses, and we offer suggestions
for how to select students who will nurture an interdisciplinary
learning environment and thrive there.
challenges. These have largely been addressed either by providing new
masters programs or by redesigning undergraduate programs. In contrast, short courses can respond to a different need: they can provide
condensed updates for professionals across academia, the clinic, and
industry. These courses have received less attention. Here, we share our
experiences in developing and providing such courses to current and
future leaders in systems biology and systems medicine. We present
guidelines for how to reproduce our courses, and we offer suggestions
for how to select students who will nurture an interdisciplinary
learning environment and thrive there.
89.
Hernandez-de-Diego, R.; de Villiers, E. P.; Klingstrom, T.; Gourle, H.; Conesa, A.; Bongcam-Rudloff, E.
The eBioKit, a stand-alone educational platform for bioinformatics Journal Article
In: PLOS COMPUTATIONAL BIOLOGY, vol. 13, no. 9, 2017, ISSN: 1553-734X.
@article{ISI:000411981000002,
title = {The eBioKit, a stand-alone educational platform for bioinformatics},
author = { R. Hernandez-de-Diego and E. P. de Villiers and T. Klingstrom and H. Gourle and A. Conesa and E. Bongcam-Rudloff},
url = {http://dx.doi.org/10.1371/journal.pcbi.1005616},
doi = {10.1371/journal.pcbi.1005616},
issn = {1553-734X},
year = {2017},
date = {2017-09-01},
journal = {PLOS COMPUTATIONAL BIOLOGY},
volume = {13},
number = {9},
abstract = {Bioinformatics skills have become essential for many research areas;
however, the availability of qualified researchers is usually lower than
the demand and training to increase the number of able bioinformaticians
is an important task for the bioinformatics community. When conducting
training or hands-on tutorials, the lack of control over the analysis
tools and repositories often results in undesirable situations during
training, as unavailable online tools or version conflicts may delay, complicate, or even prevent the successful completion of a training
event. The eBioKit is a stand-alone educational platform that hosts
numerous tools and databases for bioinformatics research and allows
training to take place in a controlled environment. A key advantage of
the eBioKit over other existing teaching solutions is that all the
required software and databases are locally installed on the system, significantly reducing the dependence on the internet. Furthermore, the
architecture of the eBioKit has demonstrated itself to be an excellent
balance between portability and performance, not only making the eBioKit
an exceptional educational tool but also providing small research groups
with a platform to incorporate bioinformatics analysis in their
research. As a result, the eBioKit has formed an integral part of
training and research performed by a wide variety of universities and
organizations such as the Pan African Bioinformatics Network (H3ABioNet)
as part of the initiative Human Heredity and Health in Africa
(H3Africa), the Southern Africa Network for Biosciences (SAnBio)
initiative, the Biosciences eastern and central Africa (BecA) hub, and
the International Glossina Genome Initiative.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bioinformatics skills have become essential for many research areas;
however, the availability of qualified researchers is usually lower than
the demand and training to increase the number of able bioinformaticians
is an important task for the bioinformatics community. When conducting
training or hands-on tutorials, the lack of control over the analysis
tools and repositories often results in undesirable situations during
training, as unavailable online tools or version conflicts may delay, complicate, or even prevent the successful completion of a training
event. The eBioKit is a stand-alone educational platform that hosts
numerous tools and databases for bioinformatics research and allows
training to take place in a controlled environment. A key advantage of
the eBioKit over other existing teaching solutions is that all the
required software and databases are locally installed on the system, significantly reducing the dependence on the internet. Furthermore, the
architecture of the eBioKit has demonstrated itself to be an excellent
balance between portability and performance, not only making the eBioKit
an exceptional educational tool but also providing small research groups
with a platform to incorporate bioinformatics analysis in their
research. As a result, the eBioKit has formed an integral part of
training and research performed by a wide variety of universities and
organizations such as the Pan African Bioinformatics Network (H3ABioNet)
as part of the initiative Human Heredity and Health in Africa
(H3Africa), the Southern Africa Network for Biosciences (SAnBio)
initiative, the Biosciences eastern and central Africa (BecA) hub, and
the International Glossina Genome Initiative.
however, the availability of qualified researchers is usually lower than
the demand and training to increase the number of able bioinformaticians
is an important task for the bioinformatics community. When conducting
training or hands-on tutorials, the lack of control over the analysis
tools and repositories often results in undesirable situations during
training, as unavailable online tools or version conflicts may delay, complicate, or even prevent the successful completion of a training
event. The eBioKit is a stand-alone educational platform that hosts
numerous tools and databases for bioinformatics research and allows
training to take place in a controlled environment. A key advantage of
the eBioKit over other existing teaching solutions is that all the
required software and databases are locally installed on the system, significantly reducing the dependence on the internet. Furthermore, the
architecture of the eBioKit has demonstrated itself to be an excellent
balance between portability and performance, not only making the eBioKit
an exceptional educational tool but also providing small research groups
with a platform to incorporate bioinformatics analysis in their
research. As a result, the eBioKit has formed an integral part of
training and research performed by a wide variety of universities and
organizations such as the Pan African Bioinformatics Network (H3ABioNet)
as part of the initiative Human Heredity and Health in Africa
(H3Africa), the Southern Africa Network for Biosciences (SAnBio)
initiative, the Biosciences eastern and central Africa (BecA) hub, and
the International Glossina Genome Initiative.
88.
Ramirez, R. N.; El-Ali, N. C.; Mager, M. A.; Wyman, D.; Conesa, A.; Mortazavi, A.
Dynamic Gene Regulatory Networks of Human Myeloid Differentiation Journal Article
In: CELL SYSTEMS, vol. 4, no. 4, pp. 416+, 2017, ISSN: 2405-4712.
@article{ISI:000402747300007,
title = {Dynamic Gene Regulatory Networks of Human Myeloid Differentiation},
author = { R. N. Ramirez and N. C. El-Ali and M. A. Mager and D. Wyman and A. Conesa and A. Mortazavi},
url = {http://dx.doi.org/10.1016/j.cels.2017.03.005},
doi = {10.1016/j.cels.2017.03.005},
issn = {2405-4712},
year = {2017},
date = {2017-04-01},
journal = {CELL SYSTEMS},
volume = {4},
number = {4},
pages = {416+},
abstract = {The reconstruction of gene regulatory networks underlying cell
differentiation from high-throughput gene expression and chromatin data
remains a challenge. Here, we derive dynamic gene regulatory networks
for human myeloid differentiation using a 5-day time series of RNA-seq
and ATAC-seq data. We profile HL-60 promyelocytes differentiating into
macrophages, neutrophils, monocytes, and monocyte-derived macrophages.
We find a rapid response in the expression of key transcription factors
and lineage markers that only regulate a subset of their targets at a
given time, which is followed by chromatin accessibility changes that
occur later along with further gene expression changes. We observe
differences between promyelocyte-and monocytederived macrophages at both
the transcriptional and chromatin landscape level, despite using the
same differentiation stimulus, which suggest that the path taken by
cells in the differentiation landscape defines their end cell state.
More generally, our approach of combining neighboring time points and
replicates to achieve greater sequencing depth can efficiently infer
footprint-based regulatory networks from long series data.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The reconstruction of gene regulatory networks underlying cell
differentiation from high-throughput gene expression and chromatin data
remains a challenge. Here, we derive dynamic gene regulatory networks
for human myeloid differentiation using a 5-day time series of RNA-seq
and ATAC-seq data. We profile HL-60 promyelocytes differentiating into
macrophages, neutrophils, monocytes, and monocyte-derived macrophages.
We find a rapid response in the expression of key transcription factors
and lineage markers that only regulate a subset of their targets at a
given time, which is followed by chromatin accessibility changes that
occur later along with further gene expression changes. We observe
differences between promyelocyte-and monocytederived macrophages at both
the transcriptional and chromatin landscape level, despite using the
same differentiation stimulus, which suggest that the path taken by
cells in the differentiation landscape defines their end cell state.
More generally, our approach of combining neighboring time points and
replicates to achieve greater sequencing depth can efficiently infer
footprint-based regulatory networks from long series data.
differentiation from high-throughput gene expression and chromatin data
remains a challenge. Here, we derive dynamic gene regulatory networks
for human myeloid differentiation using a 5-day time series of RNA-seq
and ATAC-seq data. We profile HL-60 promyelocytes differentiating into
macrophages, neutrophils, monocytes, and monocyte-derived macrophages.
We find a rapid response in the expression of key transcription factors
and lineage markers that only regulate a subset of their targets at a
given time, which is followed by chromatin accessibility changes that
occur later along with further gene expression changes. We observe
differences between promyelocyte-and monocytederived macrophages at both
the transcriptional and chromatin landscape level, despite using the
same differentiation stimulus, which suggest that the path taken by
cells in the differentiation landscape defines their end cell state.
More generally, our approach of combining neighboring time points and
replicates to achieve greater sequencing depth can efficiently infer
footprint-based regulatory networks from long series data.
87.
Sebastian-Leon, P.; Conesa, A.; Arnau, V.; Remohi, J.; Pellicer, A.; Simon, C.; Diaz-Gimeno, P.
Network Biology of Menstrual Cycle to Understand the Key Drivers of Endometrial Receptivity. Journal Article
In: REPRODUCTIVE SCIENCES, vol. 24, no. 1, pp. 162A, 2017, ISSN: 1933-7191, (64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Orlando, FL, MAR 15-18, 2017).
@article{ISI:000399043900345,
title = {Network Biology of Menstrual Cycle to Understand the Key Drivers of
Endometrial Receptivity.},
author = { P. Sebastian-Leon and A. Conesa and V. Arnau and J. Remohi and A. Pellicer and C. Simon and P. Diaz-Gimeno},
issn = {1933-7191},
year = {2017},
date = {2017-03-01},
journal = {REPRODUCTIVE SCIENCES},
volume = {24},
number = {1},
pages = {162A},
organization = {Soc Reprod Invest},
note = {64th Annual Scientific Meeting of the
Society-for-Reproductive-Investigation (SRI), Orlando, FL, MAR 15-18, 2017},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
86.
Ordonez-Baquera, P. Lucia; Gonzalez-Rodriguez, E.; Aguado-Santacruz, G. Armando; Rascon-Cruz, Q.; Conesa, A.; Moreno-Brito, V.; Echavarria, R.; Dominguez-Viveros, J.
Identification of miRNA from Bouteloua gracilis, a drought tolerant grass, by deep sequencing and their in silico analysis Journal Article
In: COMPUTATIONAL BIOLOGY AND CHEMISTRY, vol. 66, pp. 26-35, 2017, ISSN: 1476-9271.
@article{ISI:000392353200004,
title = {Identification of miRNA from Bouteloua gracilis, a drought tolerant
grass, by deep sequencing and their in silico analysis},
author = { P. Lucia Ordonez-Baquera and E. Gonzalez-Rodriguez and G. Armando Aguado-Santacruz and Q. Rascon-Cruz and A. Conesa and V. Moreno-Brito and R. Echavarria and J. Dominguez-Viveros},
url = {http://dx.doi.org/10.1016/j.compbiolchem.2016.11.001},
doi = {10.1016/j.compbiolchem.2016.11.001},
issn = {1476-9271},
year = {2017},
date = {2017-02-01},
journal = {COMPUTATIONAL BIOLOGY AND CHEMISTRY},
volume = {66},
pages = {26-35},
abstract = {Background: MicroRNAs (miRNAs) are small non-coding RNA molecules that
regulate signal transduction, development, metabolism, and stress
responses in plants through post-transcriptional degradation and/or
translational repression of target mRNAs. Several studies have addressed
the role of miRNAs in model plant species, but miRNA expression and
function in economically important forage crops, such as Bouteloua
gracilis (Poaceae), a high-quality and drought-resistant grass
distributed in semiarid regions of the United States and northern Mexico
remain unknown.
Results: We applied high-throughput sequencing technology and
bioinformatics analysis and identified 31 conserved miRNA families and
53 novel putative miRNAs with different abundance of reads in
chlorophyllic cell cultures derived from B. gracilis. Some conserved
miRNA families were highly abundant and possessed predicted targets
involved in metabolism, plant growth and development, and stress
responses. We also predicted additional identified novel miRNAs with
specific targets, including B. gracilis ESTs, which were detected under
drought stress conditions.
Conclusions: Here we report 31 conserved miRNA families and 53 putative
novel miRNAs in B. gracilis. Our results suggested the presence of
regulatory miRNAs involved in modulating physiological and stress
responses in this grass species. (C) 2016 Elsevier Ltd. All rights
reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: MicroRNAs (miRNAs) are small non-coding RNA molecules that
regulate signal transduction, development, metabolism, and stress
responses in plants through post-transcriptional degradation and/or
translational repression of target mRNAs. Several studies have addressed
the role of miRNAs in model plant species, but miRNA expression and
function in economically important forage crops, such as Bouteloua
gracilis (Poaceae), a high-quality and drought-resistant grass
distributed in semiarid regions of the United States and northern Mexico
remain unknown.
Results: We applied high-throughput sequencing technology and
bioinformatics analysis and identified 31 conserved miRNA families and
53 novel putative miRNAs with different abundance of reads in
chlorophyllic cell cultures derived from B. gracilis. Some conserved
miRNA families were highly abundant and possessed predicted targets
involved in metabolism, plant growth and development, and stress
responses. We also predicted additional identified novel miRNAs with
specific targets, including B. gracilis ESTs, which were detected under
drought stress conditions.
Conclusions: Here we report 31 conserved miRNA families and 53 putative
novel miRNAs in B. gracilis. Our results suggested the presence of
regulatory miRNAs involved in modulating physiological and stress
responses in this grass species. (C) 2016 Elsevier Ltd. All rights
reserved.
regulate signal transduction, development, metabolism, and stress
responses in plants through post-transcriptional degradation and/or
translational repression of target mRNAs. Several studies have addressed
the role of miRNAs in model plant species, but miRNA expression and
function in economically important forage crops, such as Bouteloua
gracilis (Poaceae), a high-quality and drought-resistant grass
distributed in semiarid regions of the United States and northern Mexico
remain unknown.
Results: We applied high-throughput sequencing technology and
bioinformatics analysis and identified 31 conserved miRNA families and
53 novel putative miRNAs with different abundance of reads in
chlorophyllic cell cultures derived from B. gracilis. Some conserved
miRNA families were highly abundant and possessed predicted targets
involved in metabolism, plant growth and development, and stress
responses. We also predicted additional identified novel miRNAs with
specific targets, including B. gracilis ESTs, which were detected under
drought stress conditions.
Conclusions: Here we report 31 conserved miRNA families and 53 putative
novel miRNAs in B. gracilis. Our results suggested the presence of
regulatory miRNAs involved in modulating physiological and stress
responses in this grass species. (C) 2016 Elsevier Ltd. All rights
reserved.
2016
85.
Blaustein, R.; Meyer, J.; Conesa, A.; Lorca, G.; Teplitski, M.
Impacts of abundance of Candidatus Liberibacter on the citrus phyto-microbiome Journal Article
In: PHYTOPATHOLOGY, vol. 106, no. 12, S, pp. 25-26, 2016, ISSN: 0031-949X, (Annual Meeting of the American-Phytopathological-Society (APS), Tampa, FL, JUL 30-AUG 03, 2016).
@article{ISI:000390471900128,
title = {Impacts of abundance of Candidatus Liberibacter on the citrus
phyto-microbiome},
author = { R. Blaustein and J. Meyer and A. Conesa and G. Lorca and M. Teplitski},
issn = {0031-949X},
year = {2016},
date = {2016-12-01},
journal = {PHYTOPATHOLOGY},
volume = {106},
number = {12, S},
pages = {25-26},
organization = {Amer Phytopathol Soc},
note = {Annual Meeting of the American-Phytopathological-Society (APS), Tampa, FL, JUL 30-AUG 03, 2016},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
84.
Auffray, C.; Balling, R.; Barroso, I.; Bencze, L.; Benson, M.; Bergeron, J.; Bernal-Delgado, E.; Blomberg, N.; Bock, C.; Conesa, A.; Signore, S. Del; Delogne, C.; Devilee, P.; Meglio, A. Di; Eijkemans, M.; Flicek, P.; Graf, N.; Grimm, V.; Guchelaar, H.; Guo, Y.; Gut, I. G.; Hanbury, A.; Hanif, S.; Hilgers, R.; Honrado, A.; Hose, D. R.; Houwing-Duistermaat, J.; Hubbard, T.; Janacek, S. H.; Karanikas, H.; Kievits, T.; Kohler, M.; Kremer, A.; Lanfear, J.; Lengauer, T.; Maes, E.; Meert, T.; Muller, W.; Nickel, D.; Oledzki, P.; Pedersen, B.; Petkovic, M.; Pliakos, K.; Rattray, M.; i Mas, J. Redon; Schneider, R.; Sengstag, T.; Serra-Picamal, X.; Spek, W.; Vaas, L. A. I.; van Batenburg, O.; Vandelaer, M.; Varnai, P.; Villoslada, P.; Vizcaino, J. A.; Wubbe, J. P. M.; Zanetti, G.
Making sense of big data in health research: towards an EU action plan (vol 8, pg 71, 2016) Journal Article
In: GENOME MEDICINE, vol. 8, 2016, ISSN: 1756-994X.
@article{ISI:000387621900001,
title = {Making sense of big data in health research: towards an EU action plan
(vol 8, pg 71, 2016)},
author = { C. Auffray and R. Balling and I. Barroso and L. Bencze and M. Benson and J. Bergeron and E. Bernal-Delgado and N. Blomberg and C. Bock and A. Conesa and S. Del Signore and C. Delogne and P. Devilee and A. Di Meglio and M. Eijkemans and P. Flicek and N. Graf and V. Grimm and H. Guchelaar and Y. Guo and I. G. Gut and A. Hanbury and S. Hanif and R. Hilgers and A. Honrado and D. R. Hose and J. Houwing-Duistermaat and T. Hubbard and S. H. Janacek and H. Karanikas and T. Kievits and M. Kohler and A. Kremer and J. Lanfear and T. Lengauer and E. Maes and T. Meert and W. Muller and D. Nickel and P. Oledzki and B. Pedersen and M. Petkovic and K. Pliakos and M. Rattray and J. Redon i Mas and R. Schneider and T. Sengstag and X. Serra-Picamal and W. Spek and L. A. I. Vaas and O. van Batenburg and M. Vandelaer and P. Varnai and P. Villoslada and J. A. Vizcaino and J. P. M. Wubbe and G. Zanetti},
url = {http://dx.doi.org/10.1186/s13073-016-0376-y},
doi = {10.1186/s13073-016-0376-y},
issn = {1756-994X},
year = {2016},
date = {2016-11-01},
journal = {GENOME MEDICINE},
volume = {8},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
83.
Furio-Tari, P.; Conesa, A.; Tarazona, S.
RGmatch: matching genomic regions to proximal genes in omics data integration Journal Article
In: BMC BIOINFORMATICS, vol. 17, no. 15, 2016, ISSN: 1471-2105.
@article{ISI:000392470500001,
title = {RGmatch: matching genomic regions to proximal genes in omics data
integration},
author = { P. Furio-Tari and A. Conesa and S. Tarazona},
url = {http://dx.doi.org/10.1186/s12859-016-1293-1},
doi = {10.1186/s12859-016-1293-1},
issn = {1471-2105},
year = {2016},
date = {2016-11-01},
journal = {BMC BIOINFORMATICS},
volume = {17},
number = {15},
abstract = {Background: The integrative analysis of multiple genomics data often
requires that genome coordinates-based signals have to be associated
with proximal genes. The relative location of a genomic region with
respect to the gene (gene area) is important for functional data
interpretation; hence algorithms that match regions to genes should be
able to deliver insight into this information.
Results: In this work we review the tools that are publicly available
for making region-to-gene associations. We also present a novel method, RGmatch, a flexible and easy-to-use Python tool that computes
associations either at the gene, transcript, or exon level, applying a
set of rules to annotate each region-gene association with the region
location within the gene. RGmatch can be applied to any organism as long
as genome annotation is available. Furthermore, we qualitatively and
quantitatively compare RGmatch to other tools.
Conclusions: RGmatch simplifies the association of a genomic region with
its closest gene. At the same time, it is a powerful tool because the
rules used to annotate these associations are very easy to modify
according to the researcher's specific interests. Some important
differences between RGmatch and other similar tools already in existence
are RGmatch's flexibility, its wide range of user options, compatibility
with any annotatable organism, and its comprehensive and user-friendly
output.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: The integrative analysis of multiple genomics data often
requires that genome coordinates-based signals have to be associated
with proximal genes. The relative location of a genomic region with
respect to the gene (gene area) is important for functional data
interpretation; hence algorithms that match regions to genes should be
able to deliver insight into this information.
Results: In this work we review the tools that are publicly available
for making region-to-gene associations. We also present a novel method, RGmatch, a flexible and easy-to-use Python tool that computes
associations either at the gene, transcript, or exon level, applying a
set of rules to annotate each region-gene association with the region
location within the gene. RGmatch can be applied to any organism as long
as genome annotation is available. Furthermore, we qualitatively and
quantitatively compare RGmatch to other tools.
Conclusions: RGmatch simplifies the association of a genomic region with
its closest gene. At the same time, it is a powerful tool because the
rules used to annotate these associations are very easy to modify
according to the researcher's specific interests. Some important
differences between RGmatch and other similar tools already in existence
are RGmatch's flexibility, its wide range of user options, compatibility
with any annotatable organism, and its comprehensive and user-friendly
output.
requires that genome coordinates-based signals have to be associated
with proximal genes. The relative location of a genomic region with
respect to the gene (gene area) is important for functional data
interpretation; hence algorithms that match regions to genes should be
able to deliver insight into this information.
Results: In this work we review the tools that are publicly available
for making region-to-gene associations. We also present a novel method, RGmatch, a flexible and easy-to-use Python tool that computes
associations either at the gene, transcript, or exon level, applying a
set of rules to annotate each region-gene association with the region
location within the gene. RGmatch can be applied to any organism as long
as genome annotation is available. Furthermore, we qualitatively and
quantitatively compare RGmatch to other tools.
Conclusions: RGmatch simplifies the association of a genomic region with
its closest gene. At the same time, it is a powerful tool because the
rules used to annotate these associations are very easy to modify
according to the researcher's specific interests. Some important
differences between RGmatch and other similar tools already in existence
are RGmatch's flexibility, its wide range of user options, compatibility
with any annotatable organism, and its comprehensive and user-friendly
output.
82.
Panis, D. N. De; Padro, J.; Furio-Tari, P.; Tarazona, S.; Carmona, P. S. Milla; Soto, I. M.; Dopazo, H.; Conesa, A.; Hasson, E.
Transcriptome modulation during host shift is driven by secondary metabolites in desert Drosophila Journal Article
In: MOLECULAR ECOLOGY, vol. 25, no. 18, pp. 4534-4550, 2016, ISSN: 0962-1083.
@article{ISI:000383344400010,
title = {Transcriptome modulation during host shift is driven by secondary
metabolites in desert Drosophila},
author = { D. N. De Panis and J. Padro and P. Furio-Tari and S. Tarazona and P. S. Milla Carmona and I. M. Soto and H. Dopazo and A. Conesa and E. Hasson},
url = {http://dx.doi.org/10.1111/mec.13785},
doi = {10.1111/mec.13785},
issn = {0962-1083},
year = {2016},
date = {2016-09-01},
journal = {MOLECULAR ECOLOGY},
volume = {25},
number = {18},
pages = {4534-4550},
abstract = {High-throughput transcriptome studies are breaking new ground to
investigate the responses that organisms deploy in alternative
environments. Nevertheless, much remains to be understood about the
genetic basis of host plant adaptation. Here, we investigate genome-wide
expression in the fly Drosophila buzzatii raised in different
conditions. This species uses decaying tissues of cactus of the genus
Opuntia as primary rearing substrate and secondarily, the necrotic
tissues of the columnar cactus Trichocereus terscheckii. The latter
constitutes a harmful host, rich in mescaline and other related
phenylethylamine alkaloids. We assessed the transcriptomic responses of
larvae reared in Opuntia sulphurea and T. terscheckii, with and without
the addition of alkaloids extracted from the latter. Whole-genome
expression profiles were massively modulated by the rearing environment, mainly by the presence of T. terscheckii alkaloids. Differentially
expressed genes were mainly related to detoxification, oxidation-reduction and stress response; however, we also found genes
involved in development and neurobiological processes. In conclusion, our study contributes new data onto the role of transcriptional
plasticity in response to alternative rearing environments.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
High-throughput transcriptome studies are breaking new ground to
investigate the responses that organisms deploy in alternative
environments. Nevertheless, much remains to be understood about the
genetic basis of host plant adaptation. Here, we investigate genome-wide
expression in the fly Drosophila buzzatii raised in different
conditions. This species uses decaying tissues of cactus of the genus
Opuntia as primary rearing substrate and secondarily, the necrotic
tissues of the columnar cactus Trichocereus terscheckii. The latter
constitutes a harmful host, rich in mescaline and other related
phenylethylamine alkaloids. We assessed the transcriptomic responses of
larvae reared in Opuntia sulphurea and T. terscheckii, with and without
the addition of alkaloids extracted from the latter. Whole-genome
expression profiles were massively modulated by the rearing environment, mainly by the presence of T. terscheckii alkaloids. Differentially
expressed genes were mainly related to detoxification, oxidation-reduction and stress response; however, we also found genes
involved in development and neurobiological processes. In conclusion, our study contributes new data onto the role of transcriptional
plasticity in response to alternative rearing environments.
investigate the responses that organisms deploy in alternative
environments. Nevertheless, much remains to be understood about the
genetic basis of host plant adaptation. Here, we investigate genome-wide
expression in the fly Drosophila buzzatii raised in different
conditions. This species uses decaying tissues of cactus of the genus
Opuntia as primary rearing substrate and secondarily, the necrotic
tissues of the columnar cactus Trichocereus terscheckii. The latter
constitutes a harmful host, rich in mescaline and other related
phenylethylamine alkaloids. We assessed the transcriptomic responses of
larvae reared in Opuntia sulphurea and T. terscheckii, with and without
the addition of alkaloids extracted from the latter. Whole-genome
expression profiles were massively modulated by the rearing environment, mainly by the presence of T. terscheckii alkaloids. Differentially
expressed genes were mainly related to detoxification, oxidation-reduction and stress response; however, we also found genes
involved in development and neurobiological processes. In conclusion, our study contributes new data onto the role of transcriptional
plasticity in response to alternative rearing environments.
81.
Conesa, A.; Madrigal, P.; Tarazona, S.; Gomez-Cabrero, D.; Cervera, A.; McPherson, A.; Szczesniak, M. W.; Gaffney, D. J.; Elo, L. L.; Zhang, X.; Mortazavi, A.
A survey of best practices for RNA-seq data analysis (vol 17, 13, 2016) Journal Article
In: GENOME BIOLOGY, vol. 17, 2016, ISSN: 1474-760X.
@article{ISI:000383427700002,
title = {A survey of best practices for RNA-seq data analysis (vol 17, 13, 2016)},
author = { A. Conesa and P. Madrigal and S. Tarazona and D. Gomez-Cabrero and A. Cervera and A. McPherson and M. W. Szczesniak and D. J. Gaffney and L. L. Elo and X. Zhang and A. Mortazavi},
url = {http://dx.doi.org/10.1186/s13059-016-1047-4},
doi = {10.1186/s13059-016-1047-4},
issn = {1474-760X},
year = {2016},
date = {2016-08-01},
journal = {GENOME BIOLOGY},
volume = {17},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
80.
Furio-Tari, P.; Tarazona, S.; Gabaldon, T.; Enright, A. J.; Conesa, A.
spongeScan: A web for detecting microRNA binding elements in lncRNA sequences Journal Article
In: NUCLEIC ACIDS RESEARCH, vol. 44, no. W1, pp. W176-W180, 2016, ISSN: 0305-1048.
@article{ISI:000379786800029,
title = {spongeScan: A web for detecting microRNA binding elements in lncRNA
sequences},
author = { P. Furio-Tari and S. Tarazona and T. Gabaldon and A. J. Enright and A. Conesa},
url = {http://dx.doi.org/10.1093/nar/gkw443},
doi = {10.1093/nar/gkw443},
issn = {0305-1048},
year = {2016},
date = {2016-07-01},
journal = {NUCLEIC ACIDS RESEARCH},
volume = {44},
number = {W1},
pages = {W176-W180},
abstract = {Non-coding RNA transcripts such as microRNAs (miRNAs) and long
non-coding RNAs (lncRNAs) are important genetic regulators. However, the
functions of many of these transcripts are still not clearly understood.
Recently, it has become apparent that there is significant crosstalk
between miRNAs and lncRNAs and that this creates competition for binding
between the miRNA, a lncRNA and other regulatory targets. Indeed, various competitive endogenous RNAs (ceRNAs) have already been
identified where a lncRNA acts by sequestering miRNAs. This implies the
down-regulation in the interaction of the miRNAs with their mRNA
targets, what has been called a sponge effect. Multiple approaches exist
for the prediction of miRNA targets in mRNAs. However, few methods exist
for the prediction of miRNA response elements (MREs) in lncRNAs acting
as ceRNAs (sponges). Here, we present spongeScan
(http://spongescan.rc.ufl.edu), a graphical web tool to compute and
visualize putative MREs in lncRNAs, along with different measures to
assess their likely behavior as ceRNAs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Non-coding RNA transcripts such as microRNAs (miRNAs) and long
non-coding RNAs (lncRNAs) are important genetic regulators. However, the
functions of many of these transcripts are still not clearly understood.
Recently, it has become apparent that there is significant crosstalk
between miRNAs and lncRNAs and that this creates competition for binding
between the miRNA, a lncRNA and other regulatory targets. Indeed, various competitive endogenous RNAs (ceRNAs) have already been
identified where a lncRNA acts by sequestering miRNAs. This implies the
down-regulation in the interaction of the miRNAs with their mRNA
targets, what has been called a sponge effect. Multiple approaches exist
for the prediction of miRNA targets in mRNAs. However, few methods exist
for the prediction of miRNA response elements (MREs) in lncRNAs acting
as ceRNAs (sponges). Here, we present spongeScan
(http://spongescan.rc.ufl.edu), a graphical web tool to compute and
visualize putative MREs in lncRNAs, along with different measures to
assess their likely behavior as ceRNAs.
non-coding RNAs (lncRNAs) are important genetic regulators. However, the
functions of many of these transcripts are still not clearly understood.
Recently, it has become apparent that there is significant crosstalk
between miRNAs and lncRNAs and that this creates competition for binding
between the miRNA, a lncRNA and other regulatory targets. Indeed, various competitive endogenous RNAs (ceRNAs) have already been
identified where a lncRNA acts by sequestering miRNAs. This implies the
down-regulation in the interaction of the miRNAs with their mRNA
targets, what has been called a sponge effect. Multiple approaches exist
for the prediction of miRNA targets in mRNAs. However, few methods exist
for the prediction of miRNA response elements (MREs) in lncRNAs acting
as ceRNAs (sponges). Here, we present spongeScan
(http://spongescan.rc.ufl.edu), a graphical web tool to compute and
visualize putative MREs in lncRNAs, along with different measures to
assess their likely behavior as ceRNAs.
79.
Auffray, C.; Balling, R.; Barroso, I.; Bencze, L.; Benson, M.; Bergeron, J.; Bernal-Delgado, E.; Blomberg, N.; Bock, C.; Conesa, A.; Signore, S. Del; Delogne, C.; Devilee, P.; Meglio, A. Di; Eijkemans, M.; Flicek, P.; Graf, N.; Grimm, V.; Guchelaar, H.; Guo, Y.; Gut, I. G.; Hanbury, A.; Hanif, S.; Hilgers, R.; Honrado, A.; Hose, D. R.; Houwing-Duistermaat, J.; Hubbard, T.; Janacek, S. H.; Karanikas, H.; Kievits, T.; Kohler, M.; Kremer, A.; Lanfear, J.; Lengauer, T.; Maes, E.; Meert, T.; Mueller, W.; Nickel, D.; Oledzki, P.; Pedersen, B.; Petkovic, M.; Pliakos, K.; Rattray, M.; i Mas, J. Redon; Schneider, R.; Sengstag, T.; Serra-Picamal, X.; Spek, W.; Vaas, L. A. I.; van Batenburg, O.; Vandelaer, M.; Varnai, P.; Villoslada, P.; Vizcaino, J. A.; Wubbe, J. P. M.; Zanetti, G.
Making sense of big data in health research: Towards an EU action plan Journal Article
In: GENOME MEDICINE, vol. 8, 2016, ISSN: 1756-994X.
@article{ISI:000378592900001,
title = {Making sense of big data in health research: Towards an EU action plan},
author = { C. Auffray and R. Balling and I. Barroso and L. Bencze and M. Benson and J. Bergeron and E. Bernal-Delgado and N. Blomberg and C. Bock and A. Conesa and S. Del Signore and C. Delogne and P. Devilee and A. Di Meglio and M. Eijkemans and P. Flicek and N. Graf and V. Grimm and H. Guchelaar and Y. Guo and I. G. Gut and A. Hanbury and S. Hanif and R. Hilgers and A. Honrado and D. R. Hose and J. Houwing-Duistermaat and T. Hubbard and S. H. Janacek and H. Karanikas and T. Kievits and M. Kohler and A. Kremer and J. Lanfear and T. Lengauer and E. Maes and T. Meert and W. Mueller and D. Nickel and P. Oledzki and B. Pedersen and M. Petkovic and K. Pliakos and M. Rattray and J. Redon i Mas and R. Schneider and T. Sengstag and X. Serra-Picamal and W. Spek and L. A. I. Vaas and O. van Batenburg and M. Vandelaer and P. Varnai and P. Villoslada and J. A. Vizcaino and J. P. M. Wubbe and G. Zanetti},
url = {http://dx.doi.org/10.1186/s13073-016-0323-y},
doi = {10.1186/s13073-016-0323-y},
issn = {1756-994X},
year = {2016},
date = {2016-06-01},
journal = {GENOME MEDICINE},
volume = {8},
abstract = {Medicine and healthcare are undergoing profound changes. Whole-genome
sequencing and high-resolution imaging technologies are key drivers of
this rapid and crucial transformation. Technological innovation combined
with automation and miniaturization has triggered an explosion in data
production that will soon reach exabyte proportions. How are we going to
deal with this exponential increase in data production? The potential of
``big data'' for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very
proud of its cultural diversity; however, exploitation of the data made
available through advances in genomic medicine, imaging, and a wide
range of mobile health applications or connected devices is hampered by
numerous historical, technical, legal, and political barriers. European
health systems and databases are diverse and fragmented. There is a lack
of harmonization of data formats, processing, analysis, and data
transfer, which leads to incompatibilities and lost opportunities. Legal
frameworks for data sharing are evolving. Clinicians, researchers, and
citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will
contribute to creating the European Single Market for health, which will
improve health arid healthcare for all Europearis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Medicine and healthcare are undergoing profound changes. Whole-genome
sequencing and high-resolution imaging technologies are key drivers of
this rapid and crucial transformation. Technological innovation combined
with automation and miniaturization has triggered an explosion in data
production that will soon reach exabyte proportions. How are we going to
deal with this exponential increase in data production? The potential of
``big data'' for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very
proud of its cultural diversity; however, exploitation of the data made
available through advances in genomic medicine, imaging, and a wide
range of mobile health applications or connected devices is hampered by
numerous historical, technical, legal, and political barriers. European
health systems and databases are diverse and fragmented. There is a lack
of harmonization of data formats, processing, analysis, and data
transfer, which leads to incompatibilities and lost opportunities. Legal
frameworks for data sharing are evolving. Clinicians, researchers, and
citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will
contribute to creating the European Single Market for health, which will
improve health arid healthcare for all Europearis.
sequencing and high-resolution imaging technologies are key drivers of
this rapid and crucial transformation. Technological innovation combined
with automation and miniaturization has triggered an explosion in data
production that will soon reach exabyte proportions. How are we going to
deal with this exponential increase in data production? The potential of
``big data'' for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very
proud of its cultural diversity; however, exploitation of the data made
available through advances in genomic medicine, imaging, and a wide
range of mobile health applications or connected devices is hampered by
numerous historical, technical, legal, and political barriers. European
health systems and databases are diverse and fragmented. There is a lack
of harmonization of data formats, processing, analysis, and data
transfer, which leads to incompatibilities and lost opportunities. Legal
frameworks for data sharing are evolving. Clinicians, researchers, and
citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will
contribute to creating the European Single Market for health, which will
improve health arid healthcare for all Europearis.
78.
van der Kloet, F. M.; Sebastian-Leon, P.; Conesa, A.; Smilde, A. K.; Westerhuis, J. A.
Separating common from distinctive variation Journal Article
In: BMC BIOINFORMATICS, vol. 17, no. 5, 2016, ISSN: 1471-2105, (Conference on Statistical Methods for Omics Data Integration and Analysis, Heraklion, GREECE, NOV 10-12, 2014).
@article{ISI:000381318400009,
title = {Separating common from distinctive variation},
author = { F. M. van der Kloet and P. Sebastian-Leon and A. Conesa and A. K. Smilde and J. A. Westerhuis},
url = {http://dx.doi.org/10.1186/s12859-016-1037-2},
doi = {10.1186/s12859-016-1037-2},
issn = {1471-2105},
year = {2016},
date = {2016-06-01},
journal = {BMC BIOINFORMATICS},
volume = {17},
number = {5},
abstract = {Background: Joint and individual variation explained (JIVE), distinct
and common simultaneous component analysis (DISCO) and O2-PLS, a
two-block (X-Y) latent variable regression method with an integral OSC
filter can all be used for the integrated analysis of multiple data sets
and decompose them in three terms: a low(er)-rank approximation
capturing common variation across data sets, low(er)-rank approximations
for structured variation distinctive for each data set, and residual
noise. In this paper these three methods are compared with respect to
their mathematical properties and their respective ways of defining
common and distinctive variation.
Results: The methods are all applied on simulated data and mRNA and
miRNA data-sets from GlioBlastoma Multiform (GBM) brain tumors to
examine their overlap and differences. When the common variation is
abundant, all methods are able to find the correct solution. With real
data however, complexities in the data are treated differently by the
three methods.
Conclusions: All three methods have their own approach to estimate
common and distinctive variation with their specific strength and
weaknesses. Due to their orthogonality properties and their used
algorithms their view on the data is slightly different. By assuming
orthogonality between common and distinctive, true natural or biological
phenomena that may not be orthogonal at all might be misinterpreted.},
note = {Conference on Statistical Methods for Omics Data Integration and
Analysis, Heraklion, GREECE, NOV 10-12, 2014},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Joint and individual variation explained (JIVE), distinct
and common simultaneous component analysis (DISCO) and O2-PLS, a
two-block (X-Y) latent variable regression method with an integral OSC
filter can all be used for the integrated analysis of multiple data sets
and decompose them in three terms: a low(er)-rank approximation
capturing common variation across data sets, low(er)-rank approximations
for structured variation distinctive for each data set, and residual
noise. In this paper these three methods are compared with respect to
their mathematical properties and their respective ways of defining
common and distinctive variation.
Results: The methods are all applied on simulated data and mRNA and
miRNA data-sets from GlioBlastoma Multiform (GBM) brain tumors to
examine their overlap and differences. When the common variation is
abundant, all methods are able to find the correct solution. With real
data however, complexities in the data are treated differently by the
three methods.
Conclusions: All three methods have their own approach to estimate
common and distinctive variation with their specific strength and
weaknesses. Due to their orthogonality properties and their used
algorithms their view on the data is slightly different. By assuming
orthogonality between common and distinctive, true natural or biological
phenomena that may not be orthogonal at all might be misinterpreted.
and common simultaneous component analysis (DISCO) and O2-PLS, a
two-block (X-Y) latent variable regression method with an integral OSC
filter can all be used for the integrated analysis of multiple data sets
and decompose them in three terms: a low(er)-rank approximation
capturing common variation across data sets, low(er)-rank approximations
for structured variation distinctive for each data set, and residual
noise. In this paper these three methods are compared with respect to
their mathematical properties and their respective ways of defining
common and distinctive variation.
Results: The methods are all applied on simulated data and mRNA and
miRNA data-sets from GlioBlastoma Multiform (GBM) brain tumors to
examine their overlap and differences. When the common variation is
abundant, all methods are able to find the correct solution. With real
data however, complexities in the data are treated differently by the
three methods.
Conclusions: All three methods have their own approach to estimate
common and distinctive variation with their specific strength and
weaknesses. Due to their orthogonality properties and their used
algorithms their view on the data is slightly different. By assuming
orthogonality between common and distinctive, true natural or biological
phenomena that may not be orthogonal at all might be misinterpreted.
77.
Okonechnikov, K.; Conesa, A.; Garcia-Alcalde, F.
Qualimap 2: advanced multi-sample quality control for high-throughput sequencing data Journal Article
In: BIOINFORMATICS, vol. 32, no. 2, pp. 292-294, 2016, ISSN: 1367-4803.
@article{ISI:000368360100020,
title = {Qualimap 2: advanced multi-sample quality control for high-throughput
sequencing data},
author = { K. Okonechnikov and A. Conesa and F. Garcia-Alcalde},
url = {http://dx.doi.org/10.1093/bioinformatics/btv566},
doi = {10.1093/bioinformatics/btv566},
issn = {1367-4803},
year = {2016},
date = {2016-01-01},
journal = {BIOINFORMATICS},
volume = {32},
number = {2},
pages = {292-294},
abstract = {Motivation: Detection of random errors and systematic biases is a
crucial step of a robust pipeline for processing high-throughput
sequencing (HTS) data. Bioinformatics software tools capable of
performing this task are available, either for general analysis of HTS
data or targeted to a specific sequencing technology. However, most of
the existing QC instruments only allow processing of one sample at a
time.
Results: Qualimap 2 represents a next step in the QC analysis of HTS
data. Along with comprehensive single-sample analysis of alignment data, it includes new modes that allow simultaneous processing and comparison
of multiple samples. As with the first version, the new features are
available via both graphical and command line interface. Additionally, it includes a large number of improvements proposed by the user
community.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Motivation: Detection of random errors and systematic biases is a
crucial step of a robust pipeline for processing high-throughput
sequencing (HTS) data. Bioinformatics software tools capable of
performing this task are available, either for general analysis of HTS
data or targeted to a specific sequencing technology. However, most of
the existing QC instruments only allow processing of one sample at a
time.
Results: Qualimap 2 represents a next step in the QC analysis of HTS
data. Along with comprehensive single-sample analysis of alignment data, it includes new modes that allow simultaneous processing and comparison
of multiple samples. As with the first version, the new features are
available via both graphical and command line interface. Additionally, it includes a large number of improvements proposed by the user
community.
crucial step of a robust pipeline for processing high-throughput
sequencing (HTS) data. Bioinformatics software tools capable of
performing this task are available, either for general analysis of HTS
data or targeted to a specific sequencing technology. However, most of
the existing QC instruments only allow processing of one sample at a
time.
Results: Qualimap 2 represents a next step in the QC analysis of HTS
data. Along with comprehensive single-sample analysis of alignment data, it includes new modes that allow simultaneous processing and comparison
of multiple samples. As with the first version, the new features are
available via both graphical and command line interface. Additionally, it includes a large number of improvements proposed by the user
community.
76.
Conesa, A.; Madrigal, P.; Tarazona, S.; Gomez-Cabrero, D.; Cervera, A.; McPherson, A.; Szczesniak, M. W.; Gaffney, D. J.; Elo, L. L.; Zhang, X.; Mortazavi, A.
A survey of best practices for RNA-seq data analysis Journal Article
In: GENOME BIOLOGY, vol. 17, 2016, ISSN: 1474-760X.
@article{ISI:000368903900004,
title = {A survey of best practices for RNA-seq data analysis},
author = { A. Conesa and P. Madrigal and S. Tarazona and D. Gomez-Cabrero and A. Cervera and A. McPherson and M. W. Szczesniak and D. J. Gaffney and L. L. Elo and X. Zhang and A. Mortazavi},
url = {http://dx.doi.org/10.1186/s13059-016-0881-8},
doi = {10.1186/s13059-016-0881-8},
issn = {1474-760X},
year = {2016},
date = {2016-01-01},
journal = {GENOME BIOLOGY},
volume = {17},
abstract = {RNA-sequencing (RNA-seq) has a wide variety of applications, but no
single analysis pipeline can be used in all cases. We review all of the
major steps in RNA-seq data analysis, including experimental design, quality control, read alignment, quantification of gene and transcript
levels, visualization, differential gene expression, alternative
splicing, functional analysis, gene fusion detection and eQTL mapping.
We highlight the challenges associated with each step. We discuss the
analysis of small RNAs and the integration of RNA-seq with other
functional genomics techniques. Finally, we discuss the outlook for
novel technologies that are changing the state of the art in
transcriptomics.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
RNA-sequencing (RNA-seq) has a wide variety of applications, but no
single analysis pipeline can be used in all cases. We review all of the
major steps in RNA-seq data analysis, including experimental design, quality control, read alignment, quantification of gene and transcript
levels, visualization, differential gene expression, alternative
splicing, functional analysis, gene fusion detection and eQTL mapping.
We highlight the challenges associated with each step. We discuss the
analysis of small RNAs and the integration of RNA-seq with other
functional genomics techniques. Finally, we discuss the outlook for
novel technologies that are changing the state of the art in
transcriptomics.
single analysis pipeline can be used in all cases. We review all of the
major steps in RNA-seq data analysis, including experimental design, quality control, read alignment, quantification of gene and transcript
levels, visualization, differential gene expression, alternative
splicing, functional analysis, gene fusion detection and eQTL mapping.
We highlight the challenges associated with each step. We discuss the
analysis of small RNAs and the integration of RNA-seq with other
functional genomics techniques. Finally, we discuss the outlook for
novel technologies that are changing the state of the art in
transcriptomics.
2015
75.
Tarazona, S.; Furio-Tari, P.; Turra, D.; Pietro, A. Di; Nueda, M. Jose; Ferrer, A.; Conesa, A.
Data quality aware analysis of differential expression in RNA-seq with NOISeq R/Bioc package Journal Article
In: NUCLEIC ACIDS RESEARCH, vol. 43, no. 21, 2015, ISSN: 0305-1048.
@article{ISI:000366410900003,
title = {Data quality aware analysis of differential expression in RNA-seq with
NOISeq R/Bioc package},
author = { S. Tarazona and P. Furio-Tari and D. Turra and A. Di Pietro and M. Jose Nueda and A. Ferrer and A. Conesa},
url = {http://dx.doi.org/10.1093/nar/gkv711},
doi = {10.1093/nar/gkv711},
issn = {0305-1048},
year = {2015},
date = {2015-12-01},
journal = {NUCLEIC ACIDS RESEARCH},
volume = {43},
number = {21},
abstract = {As the use of RNA-seq has popularized, there is an increasing
consciousness of the importance of experimental design, bias removal, accurate quantification and control of false positives for proper data
analysis. We introduce the NOISeq R-package for quality control and
analysis of count data. We show how the available diagnostic tools can
be used to monitor quality issues, make pre-processing decisions and
improve analysis. We demonstrate that the nonparametric NOISeqBIO
efficiently controls false discoveries in experiments with biological
replication and outperforms state-of-the-art methods. NOISeq is a
comprehensive resource that meets current needs for robust data-aware
analysis of RNA-seq differential expression.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
As the use of RNA-seq has popularized, there is an increasing
consciousness of the importance of experimental design, bias removal, accurate quantification and control of false positives for proper data
analysis. We introduce the NOISeq R-package for quality control and
analysis of count data. We show how the available diagnostic tools can
be used to monitor quality issues, make pre-processing decisions and
improve analysis. We demonstrate that the nonparametric NOISeqBIO
efficiently controls false discoveries in experiments with biological
replication and outperforms state-of-the-art methods. NOISeq is a
comprehensive resource that meets current needs for robust data-aware
analysis of RNA-seq differential expression.
consciousness of the importance of experimental design, bias removal, accurate quantification and control of false positives for proper data
analysis. We introduce the NOISeq R-package for quality control and
analysis of count data. We show how the available diagnostic tools can
be used to monitor quality issues, make pre-processing decisions and
improve analysis. We demonstrate that the nonparametric NOISeqBIO
efficiently controls false discoveries in experiments with biological
replication and outperforms state-of-the-art methods. NOISeq is a
comprehensive resource that meets current needs for robust data-aware
analysis of RNA-seq differential expression.
74.
Conesa-Zamora, P.; Garcia-Solano, J.; del Carmen Turpin, M.; Sebastian-Leon, P.; Torres-Moreno, D.; Estrada, E.; Tuomisto, A.; Wilce, J.; Maekinen, M. J.; Perez-Guillermo, M.; Conesa, A.
Methylome profiling reveals functions and genes which are differentially methylated in serrated compared to conventional colorectal carcinoma Journal Article
In: CLINICAL EPIGENETICS, vol. 7, 2015, ISSN: 1868-7083.
@article{ISI:000361363000001,
title = {Methylome profiling reveals functions and genes which are differentially
methylated in serrated compared to conventional colorectal carcinoma},
author = { P. Conesa-Zamora and J. Garcia-Solano and M. del Carmen Turpin and P. Sebastian-Leon and D. Torres-Moreno and E. Estrada and A. Tuomisto and J. Wilce and M. J. Maekinen and M. Perez-Guillermo and A. Conesa},
url = {http://dx.doi.org/10.1186/s13148-015-0128-7},
doi = {10.1186/s13148-015-0128-7},
issn = {1868-7083},
year = {2015},
date = {2015-09-01},
journal = {CLINICAL EPIGENETICS},
volume = {7},
abstract = {Background: Serrated adenocarcinoma (SAC) is a recently recognized
colorectal cancer (CRC) subtype accounting for 7.5-8.7 % of CRCs. It
has been shown that SAC has a worse prognosis and different histological
and molecular features compared to conventional carcinoma (CC) but, to
date, there is no study analysing its methylome profile.
Results: The methylation status of 450,000 CpG sites using the Infinium
Human Methylation 450 BeadChip array was investigated in 103 colorectal
specimens, including 39 SACs and 34 matched CCs, from Spanish and
Finnish patients. Microarray data showed a higher representation of
morphogenesis-, neurogenesis-, cytoskeleton-and vesicle
transport-related functions and also significant differential
methylation of 15 genes, including the iodothyronine deiodinase DIO3 and
the forkhead family transcription factor FOXD2 genes which were
validated at the CpG, mRNA and protein level using pyrosequencing, methylation-specific PCR, quantitative polymerase chain reaction (qPCR)
and immunohistochemistry. A quantification study of the methylation
status of CpG sequences in FOXD2 demonstrated a novel region controlling
gene expression. Moreover, differences in these markers were also
evident when comparing SAC with CRC showing molecular and histological
features of high-level microsatellite instability.
Conclusions: This methylome study demonstrates distinct epigenetic
regulation patterns in SAC which are consistent to previous expression
profile studies and that DIO3 and FOXD2 might be molecular targets for a
specific histology-oriented treatment of CRC.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Serrated adenocarcinoma (SAC) is a recently recognized
colorectal cancer (CRC) subtype accounting for 7.5-8.7 % of CRCs. It
has been shown that SAC has a worse prognosis and different histological
and molecular features compared to conventional carcinoma (CC) but, to
date, there is no study analysing its methylome profile.
Results: The methylation status of 450,000 CpG sites using the Infinium
Human Methylation 450 BeadChip array was investigated in 103 colorectal
specimens, including 39 SACs and 34 matched CCs, from Spanish and
Finnish patients. Microarray data showed a higher representation of
morphogenesis-, neurogenesis-, cytoskeleton-and vesicle
transport-related functions and also significant differential
methylation of 15 genes, including the iodothyronine deiodinase DIO3 and
the forkhead family transcription factor FOXD2 genes which were
validated at the CpG, mRNA and protein level using pyrosequencing, methylation-specific PCR, quantitative polymerase chain reaction (qPCR)
and immunohistochemistry. A quantification study of the methylation
status of CpG sequences in FOXD2 demonstrated a novel region controlling
gene expression. Moreover, differences in these markers were also
evident when comparing SAC with CRC showing molecular and histological
features of high-level microsatellite instability.
Conclusions: This methylome study demonstrates distinct epigenetic
regulation patterns in SAC which are consistent to previous expression
profile studies and that DIO3 and FOXD2 might be molecular targets for a
specific histology-oriented treatment of CRC.
colorectal cancer (CRC) subtype accounting for 7.5-8.7 % of CRCs. It
has been shown that SAC has a worse prognosis and different histological
and molecular features compared to conventional carcinoma (CC) but, to
date, there is no study analysing its methylome profile.
Results: The methylation status of 450,000 CpG sites using the Infinium
Human Methylation 450 BeadChip array was investigated in 103 colorectal
specimens, including 39 SACs and 34 matched CCs, from Spanish and
Finnish patients. Microarray data showed a higher representation of
morphogenesis-, neurogenesis-, cytoskeleton-and vesicle
transport-related functions and also significant differential
methylation of 15 genes, including the iodothyronine deiodinase DIO3 and
the forkhead family transcription factor FOXD2 genes which were
validated at the CpG, mRNA and protein level using pyrosequencing, methylation-specific PCR, quantitative polymerase chain reaction (qPCR)
and immunohistochemistry. A quantification study of the methylation
status of CpG sequences in FOXD2 demonstrated a novel region controlling
gene expression. Moreover, differences in these markers were also
evident when comparing SAC with CRC showing molecular and histological
features of high-level microsatellite instability.
Conclusions: This methylome study demonstrates distinct epigenetic
regulation patterns in SAC which are consistent to previous expression
profile studies and that DIO3 and FOXD2 might be molecular targets for a
specific histology-oriented treatment of CRC.
73.
Morin-Adeline, V.; Mueller, K.; Conesa, A.; Slapeta, J.
In: VETERINARY PARASITOLOGY, vol. 212, no. 3-4, pp. 111-117, 2015, ISSN: 0304-4017.
@article{ISI:000363355400007,
title = {Comparative RNA-seq analysis of the Tritrichomonas foetus PIG30/1
isolate from pigs reveals close association with Tritrichomonas foetus
BP-4 isolate `bovine genotype'},
author = { V. Morin-Adeline and K. Mueller and A. Conesa and J. Slapeta},
url = {http://dx.doi.org/10.1016/j.vetpar.2015.08.012},
doi = {10.1016/j.vetpar.2015.08.012},
issn = {0304-4017},
year = {2015},
date = {2015-09-01},
journal = {VETERINARY PARASITOLOGY},
volume = {212},
number = {3-4},
pages = {111-117},
abstract = {Tritrichomonas foetus was described as a commensal of the stomach, caecum and nasal cavity of pigs before it was recognised as the cause of
reproductive tract disease of cattle. T. foetus also causes chronic
large bowel diarrhoea in domestic cats. Multi-locus genotyping and
comparative transcriptome analysis has previously revealed that T.
foetus isolated from cat and cattle hosts are genetically distinct, referred to as the `feline genotype' and `bovine genotype', respectively. Conversely, multi-locus genotyping has grouped porcine T.
foetus with the `bovine genotype'. To compare the extent of the
similarity between porcine T. foetus and cattle `bovine genotype'
isolates, RNA-sequencing (RNA-seq) was used to produce the first
cell-wide transcriptome library of porcine T. foetus PIG30/1.
Comparative transcriptome analysis of the PIG30/1 with the published
bovine (BP-4) and feline (G10/1) transcriptomes revealed that the
porcine T. foetus shares a 4.7 fold greater number of orthologous genes
with the bovine T. foetus than with the feline T. foetus. Comparing
transcription of the virulence factors, cysteine proteases (CP) between
the three isolates, the porcine T. foetus was found to preferentially
transcribe CP8 like the `bovine genotype' T. foetus, compared to thehigh
transcription of CP7 seen for `feline genotype' T. foetus. At the
cell-wide transcriptome level, the porcine T. foetus isolate (PIG30/1)
groups closer with the `bovine genotype' T. foetus rather than the
`feline genotype' T. foetus. (C) 2015 Elsevier B.V. All rights reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Tritrichomonas foetus was described as a commensal of the stomach, caecum and nasal cavity of pigs before it was recognised as the cause of
reproductive tract disease of cattle. T. foetus also causes chronic
large bowel diarrhoea in domestic cats. Multi-locus genotyping and
comparative transcriptome analysis has previously revealed that T.
foetus isolated from cat and cattle hosts are genetically distinct, referred to as the `feline genotype' and `bovine genotype', respectively. Conversely, multi-locus genotyping has grouped porcine T.
foetus with the `bovine genotype'. To compare the extent of the
similarity between porcine T. foetus and cattle `bovine genotype'
isolates, RNA-sequencing (RNA-seq) was used to produce the first
cell-wide transcriptome library of porcine T. foetus PIG30/1.
Comparative transcriptome analysis of the PIG30/1 with the published
bovine (BP-4) and feline (G10/1) transcriptomes revealed that the
porcine T. foetus shares a 4.7 fold greater number of orthologous genes
with the bovine T. foetus than with the feline T. foetus. Comparing
transcription of the virulence factors, cysteine proteases (CP) between
the three isolates, the porcine T. foetus was found to preferentially
transcribe CP8 like the `bovine genotype' T. foetus, compared to thehigh
transcription of CP7 seen for `feline genotype' T. foetus. At the
cell-wide transcriptome level, the porcine T. foetus isolate (PIG30/1)
groups closer with the `bovine genotype' T. foetus rather than the
`feline genotype' T. foetus. (C) 2015 Elsevier B.V. All rights reserved.
reproductive tract disease of cattle. T. foetus also causes chronic
large bowel diarrhoea in domestic cats. Multi-locus genotyping and
comparative transcriptome analysis has previously revealed that T.
foetus isolated from cat and cattle hosts are genetically distinct, referred to as the `feline genotype' and `bovine genotype', respectively. Conversely, multi-locus genotyping has grouped porcine T.
foetus with the `bovine genotype'. To compare the extent of the
similarity between porcine T. foetus and cattle `bovine genotype'
isolates, RNA-sequencing (RNA-seq) was used to produce the first
cell-wide transcriptome library of porcine T. foetus PIG30/1.
Comparative transcriptome analysis of the PIG30/1 with the published
bovine (BP-4) and feline (G10/1) transcriptomes revealed that the
porcine T. foetus shares a 4.7 fold greater number of orthologous genes
with the bovine T. foetus than with the feline T. foetus. Comparing
transcription of the virulence factors, cysteine proteases (CP) between
the three isolates, the porcine T. foetus was found to preferentially
transcribe CP8 like the `bovine genotype' T. foetus, compared to thehigh
transcription of CP7 seen for `feline genotype' T. foetus. At the
cell-wide transcriptome level, the porcine T. foetus isolate (PIG30/1)
groups closer with the `bovine genotype' T. foetus rather than the
`feline genotype' T. foetus. (C) 2015 Elsevier B.V. All rights reserved.
72.
Irmer, H.; Tarazona, S.; Sasse, C.; Olbermann, P.; Loeffler, J.; Krappmann, S.; Conesa, A.; Braus, G. H.
RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see resting stage behavior Journal Article
In: BMC GENOMICS, vol. 16, 2015, ISSN: 1471-2164.
@article{ISI:000360039300003,
title = {RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait
and see resting stage behavior},
author = { H. Irmer and S. Tarazona and C. Sasse and P. Olbermann and J. Loeffler and S. Krappmann and A. Conesa and G. H. Braus},
url = {http://dx.doi.org/10.1186/s12864-015-1853-1},
doi = {10.1186/s12864-015-1853-1},
issn = {1471-2164},
year = {2015},
date = {2015-08-01},
journal = {BMC GENOMICS},
volume = {16},
abstract = {Background: Invasive aspergillosis is started after germination of
Aspergillus fumigatus conidia that are inhaled by susceptible
individuals. Fungal hyphae can grow in the lung through the epithelial
tissue and disseminate hematogenously to invade into other organs. Low
fungaemia indicates that fungal elements do not reside in the
bloodstream for long.
Results: We analyzed whether blood represents a hostile environment to
which the physiology of A. fumigatus has to adapt. An in vitro model of
A. fumigatus infection was established by incubating mycelium in blood.
Our model allowed to discern the changes of the gene expression profile
of A. fumigatus at various stages of the infection. The majority of
described virulence factors that are connected to pulmonary infections
appeared not to be activated during the blood phase. Three active
processes were identified that presumably help the fungus to survive the
blood environment in an advanced phase of the infection: iron
homeostasis, secondary metabolism, and the formation of detoxifying
enzymes.
Conclusions: We propose that A. fumigatus is hardly able to propagate in
blood. After an early stage of sensing the environment, virtually all
uptake mechanisms and energy-consuming metabolic pathways are shut-down.
The fungus appears to adapt by trans-differentiation into a resting
mycelial stage. This might reflect the harsh conditions in blood where
A. fumigatus cannot take up sufficient nutrients to establish
self-defense mechanisms combined with significant growth.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Invasive aspergillosis is started after germination of
Aspergillus fumigatus conidia that are inhaled by susceptible
individuals. Fungal hyphae can grow in the lung through the epithelial
tissue and disseminate hematogenously to invade into other organs. Low
fungaemia indicates that fungal elements do not reside in the
bloodstream for long.
Results: We analyzed whether blood represents a hostile environment to
which the physiology of A. fumigatus has to adapt. An in vitro model of
A. fumigatus infection was established by incubating mycelium in blood.
Our model allowed to discern the changes of the gene expression profile
of A. fumigatus at various stages of the infection. The majority of
described virulence factors that are connected to pulmonary infections
appeared not to be activated during the blood phase. Three active
processes were identified that presumably help the fungus to survive the
blood environment in an advanced phase of the infection: iron
homeostasis, secondary metabolism, and the formation of detoxifying
enzymes.
Conclusions: We propose that A. fumigatus is hardly able to propagate in
blood. After an early stage of sensing the environment, virtually all
uptake mechanisms and energy-consuming metabolic pathways are shut-down.
The fungus appears to adapt by trans-differentiation into a resting
mycelial stage. This might reflect the harsh conditions in blood where
A. fumigatus cannot take up sufficient nutrients to establish
self-defense mechanisms combined with significant growth.
Aspergillus fumigatus conidia that are inhaled by susceptible
individuals. Fungal hyphae can grow in the lung through the epithelial
tissue and disseminate hematogenously to invade into other organs. Low
fungaemia indicates that fungal elements do not reside in the
bloodstream for long.
Results: We analyzed whether blood represents a hostile environment to
which the physiology of A. fumigatus has to adapt. An in vitro model of
A. fumigatus infection was established by incubating mycelium in blood.
Our model allowed to discern the changes of the gene expression profile
of A. fumigatus at various stages of the infection. The majority of
described virulence factors that are connected to pulmonary infections
appeared not to be activated during the blood phase. Three active
processes were identified that presumably help the fungus to survive the
blood environment in an advanced phase of the infection: iron
homeostasis, secondary metabolism, and the formation of detoxifying
enzymes.
Conclusions: We propose that A. fumigatus is hardly able to propagate in
blood. After an early stage of sensing the environment, virtually all
uptake mechanisms and energy-consuming metabolic pathways are shut-down.
The fungus appears to adapt by trans-differentiation into a resting
mycelial stage. This might reflect the harsh conditions in blood where
A. fumigatus cannot take up sufficient nutrients to establish
self-defense mechanisms combined with significant growth.
71.
de la Fuente, L.; Conesa, A.; Lloret, A.; Badenes, M. Luisa; Rios, G.
Genome-wide changes in histone H3 lysine 27 trimethylation associated with bud dormancy release in peach Journal Article
In: TREE GENETICS & GENOMES, vol. 11, no. 3, 2015, ISSN: 1614-2942.
@article{ISI:000355704700013,
title = {Genome-wide changes in histone H3 lysine 27 trimethylation associated
with bud dormancy release in peach},
author = { L. de la Fuente and A. Conesa and A. Lloret and M. Luisa Badenes and G. Rios},
url = {http://dx.doi.org/10.1007/s11295-015-0869-7},
doi = {10.1007/s11295-015-0869-7},
issn = {1614-2942},
year = {2015},
date = {2015-06-01},
journal = {TREE GENETICS & GENOMES},
volume = {11},
number = {3},
abstract = {Bud dormancy is an evolutionary adaptation of perennial plants to the
seasonal fluctuation of temperatures in temperate climates, affected by
intrinsic and environmental signals. Recent investigations point to a
relevant role of epigenetic mechanisms in the regulation of bud
dormancy. We have performed a chromatin immunoprecipitation sequencing
(ChIP-seq) analysis of histone H3 lysine-27 trimethylation (H3K27me3), a
chromatin mark associated with stable gene silencing, in dormant (D) and
dormancy-released (ND) buds of peach (Prunus persica). H3K27me3 regions
were more abundant in gene-rich euchromatic zones of chromosomes and
associated with gene bodies. The dormancy regulators DORMANCY-ASSOCIATED
MADS-box (DAM) 1, DAM4, DAM5 and DAM6 were found significantly enriched
in H3K27me3 in ND samples, in close agreement with their
dormancy-specific expression. The DAM locus was modified at specific
short regions, allowing the uneven regulation of distinct DAM genes.
Additional regulatory factors related to meristem activity and flowering
genes from Arabidopsis thaliana were differentially H3K27 trimethylated, which suggests that meristem reactivation and flower development could
be also epigenetically regulated in reproductive buds of peach. A (GA)n
motif and CACTA-type transposon-related sequences were found
over-represented in H3K27me3 regions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bud dormancy is an evolutionary adaptation of perennial plants to the
seasonal fluctuation of temperatures in temperate climates, affected by
intrinsic and environmental signals. Recent investigations point to a
relevant role of epigenetic mechanisms in the regulation of bud
dormancy. We have performed a chromatin immunoprecipitation sequencing
(ChIP-seq) analysis of histone H3 lysine-27 trimethylation (H3K27me3), a
chromatin mark associated with stable gene silencing, in dormant (D) and
dormancy-released (ND) buds of peach (Prunus persica). H3K27me3 regions
were more abundant in gene-rich euchromatic zones of chromosomes and
associated with gene bodies. The dormancy regulators DORMANCY-ASSOCIATED
MADS-box (DAM) 1, DAM4, DAM5 and DAM6 were found significantly enriched
in H3K27me3 in ND samples, in close agreement with their
dormancy-specific expression. The DAM locus was modified at specific
short regions, allowing the uneven regulation of distinct DAM genes.
Additional regulatory factors related to meristem activity and flowering
genes from Arabidopsis thaliana were differentially H3K27 trimethylated, which suggests that meristem reactivation and flower development could
be also epigenetically regulated in reproductive buds of peach. A (GA)n
motif and CACTA-type transposon-related sequences were found
over-represented in H3K27me3 regions.
seasonal fluctuation of temperatures in temperate climates, affected by
intrinsic and environmental signals. Recent investigations point to a
relevant role of epigenetic mechanisms in the regulation of bud
dormancy. We have performed a chromatin immunoprecipitation sequencing
(ChIP-seq) analysis of histone H3 lysine-27 trimethylation (H3K27me3), a
chromatin mark associated with stable gene silencing, in dormant (D) and
dormancy-released (ND) buds of peach (Prunus persica). H3K27me3 regions
were more abundant in gene-rich euchromatic zones of chromosomes and
associated with gene bodies. The dormancy regulators DORMANCY-ASSOCIATED
MADS-box (DAM) 1, DAM4, DAM5 and DAM6 were found significantly enriched
in H3K27me3 in ND samples, in close agreement with their
dormancy-specific expression. The DAM locus was modified at specific
short regions, allowing the uneven regulation of distinct DAM genes.
Additional regulatory factors related to meristem activity and flowering
genes from Arabidopsis thaliana were differentially H3K27 trimethylated, which suggests that meristem reactivation and flower development could
be also epigenetically regulated in reproductive buds of peach. A (GA)n
motif and CACTA-type transposon-related sequences were found
over-represented in H3K27me3 regions.
70.
Yanez, Y.; Grau, E.; Rodriguez-Cortez, V. C.; Hervas, D.; Vidal, E.; Noguera, R.; Hernandez, M.; Segura, V.; Canete, A.; Conesa, A.; de Mora, J. Font; Castel, V.
Two independent epigenetic biomarkers predict survival in neuroblastoma Journal Article
In: CLINICAL EPIGENETICS, vol. 7, 2015, ISSN: 1868-7083.
@article{ISI:000350585600002,
title = {Two independent epigenetic biomarkers predict survival in neuroblastoma},
author = { Y. Yanez and E. Grau and V. C. Rodriguez-Cortez and D. Hervas and E. Vidal and R. Noguera and M. Hernandez and V. Segura and A. Canete and A. Conesa and J. Font de Mora and V. Castel},
url = {http://dx.doi.org/10.1186/s13148-015-0054-8},
doi = {10.1186/s13148-015-0054-8},
issn = {1868-7083},
year = {2015},
date = {2015-02-01},
journal = {CLINICAL EPIGENETICS},
volume = {7},
abstract = {Background: Neuroblastoma (NB) is the most common extracranial pediatric
solid tumor with a highly variable clinical course, ranging from
spontaneous regression to life-threatening disease. Survival rates for
high-risk NB patients remain disappointingly low despite multimodal
treatment. Thus, there is an urgent clinical need for additional
biomarkers to improve risk stratification, treatment management, and
survival rates in children with aggressive NB.
Results: Using gene promoter methylation analysis in 48 neuroblastoma
tumors with microarray technology, we found a strong association between survival and gene promoter hypermethylation (P = 0.036).
Hypermethylation of 70 genes significantly differentiated high-risk
survivor patients from those who died during follow-up time. Sixteen
genes with relevant roles in cancer biology were further validated in an
additional cohort of 83 neuroblastoma tumors by bisulfite
pyrosequencing. High promoter methylation rates of these genes were
found in patients with metastatic tumors (either stage metastatic (M) or
metastatic special (MS)), 18 months or older at first diagnosis, MYCN
amplification, relapsed, and dead. Notably, the degree of methylation of
retinoblastoma 1 (RB1) and teratocarcinoma-derived growth factor 1
(TDGF1) predicts event-free and overall survival independently of the
established risk factors. In addition, low RB1 mRNA expression levels
associate with poor prognosis suggesting that promoter methylation could
contribute to the transcriptional silencing of this gene in NB.
Conclusions: We found a new epigenetic signature predictive for NB
patients' outcome: the methylation status of RB1 and TDGF1 associate
with poorer survival. This information is useful to assess prognosis and
improve treatment selection.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Neuroblastoma (NB) is the most common extracranial pediatric
solid tumor with a highly variable clinical course, ranging from
spontaneous regression to life-threatening disease. Survival rates for
high-risk NB patients remain disappointingly low despite multimodal
treatment. Thus, there is an urgent clinical need for additional
biomarkers to improve risk stratification, treatment management, and
survival rates in children with aggressive NB.
Results: Using gene promoter methylation analysis in 48 neuroblastoma
tumors with microarray technology, we found a strong association between survival and gene promoter hypermethylation (P = 0.036).
Hypermethylation of 70 genes significantly differentiated high-risk
survivor patients from those who died during follow-up time. Sixteen
genes with relevant roles in cancer biology were further validated in an
additional cohort of 83 neuroblastoma tumors by bisulfite
pyrosequencing. High promoter methylation rates of these genes were
found in patients with metastatic tumors (either stage metastatic (M) or
metastatic special (MS)), 18 months or older at first diagnosis, MYCN
amplification, relapsed, and dead. Notably, the degree of methylation of
retinoblastoma 1 (RB1) and teratocarcinoma-derived growth factor 1
(TDGF1) predicts event-free and overall survival independently of the
established risk factors. In addition, low RB1 mRNA expression levels
associate with poor prognosis suggesting that promoter methylation could
contribute to the transcriptional silencing of this gene in NB.
Conclusions: We found a new epigenetic signature predictive for NB
patients' outcome: the methylation status of RB1 and TDGF1 associate
with poorer survival. This information is useful to assess prognosis and
improve treatment selection.
solid tumor with a highly variable clinical course, ranging from
spontaneous regression to life-threatening disease. Survival rates for
high-risk NB patients remain disappointingly low despite multimodal
treatment. Thus, there is an urgent clinical need for additional
biomarkers to improve risk stratification, treatment management, and
survival rates in children with aggressive NB.
Results: Using gene promoter methylation analysis in 48 neuroblastoma
tumors with microarray technology, we found a strong association between survival and gene promoter hypermethylation (P = 0.036).
Hypermethylation of 70 genes significantly differentiated high-risk
survivor patients from those who died during follow-up time. Sixteen
genes with relevant roles in cancer biology were further validated in an
additional cohort of 83 neuroblastoma tumors by bisulfite
pyrosequencing. High promoter methylation rates of these genes were
found in patients with metastatic tumors (either stage metastatic (M) or
metastatic special (MS)), 18 months or older at first diagnosis, MYCN
amplification, relapsed, and dead. Notably, the degree of methylation of
retinoblastoma 1 (RB1) and teratocarcinoma-derived growth factor 1
(TDGF1) predicts event-free and overall survival independently of the
established risk factors. In addition, low RB1 mRNA expression levels
associate with poor prognosis suggesting that promoter methylation could
contribute to the transcriptional silencing of this gene in NB.
Conclusions: We found a new epigenetic signature predictive for NB
patients' outcome: the methylation status of RB1 and TDGF1 associate
with poorer survival. This information is useful to assess prognosis and
improve treatment selection.
2014
69.
Morin-Adeline, V.; Lomas, R.; O'Meally, D.; Stack, C.; Conesa, A.; Slapeta, J.
In: BMC GENOMICS, vol. 15, 2014, ISSN: 1471-2164.
@article{ISI:000345790500001,
title = {Comparative transcriptomics reveals striking similarities between the
bovine and feline isolates of Tritrichomonas foetus: consequences for in
silico drug-target identification},
author = { V. Morin-Adeline and R. Lomas and D. O'Meally and C. Stack and A. Conesa and J. Slapeta},
url = {http://dx.doi.org/10.1186/1471-2164-15-955},
doi = {10.1186/1471-2164-15-955},
issn = {1471-2164},
year = {2014},
date = {2014-11-01},
journal = {BMC GENOMICS},
volume = {15},
abstract = {Background: Few, if any, protozoan parasites are reported to exhibit
extreme organ tropism like the flagellate Tritrichomonas foetus. In
cattle, T. foetus infects the reproductive system causing abortion, whereas the infection in cats results in chronic large bowel diarrhoea.
In the absence of a T. foetus genome, we utilized a de novo approach to
assemble the transcriptome of the bovine and feline genotype to identify
host-specific adaptations and virulence factors specific to each
genotype. Furthermore, a subset of orthologs was used to characterize
putative druggable targets and expose complications of in silico drug
target mining in species with indefinite host-ranges.
Results: Illumina RNA-seq reads were assembled into two representative
bovine and feline transcriptomes containing 42,363 and 36,559 contigs, respectively. Coding and non-coding regions of the genome libraries
revealed striking similarities, with 24,620 shared homolog pairs reduced
down to 7,547 coding orthologs between the two genotypes. The
transcriptomes were near identical in functional category distribution;
with no indication of selective pressure acting on orthologs despite
differences in parasite origins/host. Orthologs formed a large
proportion of highly expressed transcripts in both genotypes (bovine
genotype: 76%, feline genotype: 56%). Mining the libraries for
protease virulence factors revealed the cysteine proteases (CP) to be
the most common. In total, 483 and 445 bovine and feline T. foetus
transcripts were identified as putative proteases based on MEROPS
database, with 9 hits to putative protease inhibitors. In bovine T.
foetus, CP8 is the preferentially transcribed CP while in the feline
genotype, transcription of CP7 showed higher abundance. In silico
druggability analysis of the two genotypes revealed that when host
sequences are taken into account, drug targets are genotype-specific.
Conclusion: Gene discovery analysis based on RNA-seq data analysis
revealed prominent similarities between the bovine and feline T. foetus, suggesting recent adaptation to their respective host/niche. T. foetus
represents a unique case of a mammalian protozoan expanding its
parasitic grasp across distantly related host lineages. Consequences of
the host-range for in silico drug targeting are exposed here, demonstrating that targets of the parasite in one host are not
necessarily ideal for the same parasite in another host.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Few, if any, protozoan parasites are reported to exhibit
extreme organ tropism like the flagellate Tritrichomonas foetus. In
cattle, T. foetus infects the reproductive system causing abortion, whereas the infection in cats results in chronic large bowel diarrhoea.
In the absence of a T. foetus genome, we utilized a de novo approach to
assemble the transcriptome of the bovine and feline genotype to identify
host-specific adaptations and virulence factors specific to each
genotype. Furthermore, a subset of orthologs was used to characterize
putative druggable targets and expose complications of in silico drug
target mining in species with indefinite host-ranges.
Results: Illumina RNA-seq reads were assembled into two representative
bovine and feline transcriptomes containing 42,363 and 36,559 contigs, respectively. Coding and non-coding regions of the genome libraries
revealed striking similarities, with 24,620 shared homolog pairs reduced
down to 7,547 coding orthologs between the two genotypes. The
transcriptomes were near identical in functional category distribution;
with no indication of selective pressure acting on orthologs despite
differences in parasite origins/host. Orthologs formed a large
proportion of highly expressed transcripts in both genotypes (bovine
genotype: 76%, feline genotype: 56%). Mining the libraries for
protease virulence factors revealed the cysteine proteases (CP) to be
the most common. In total, 483 and 445 bovine and feline T. foetus
transcripts were identified as putative proteases based on MEROPS
database, with 9 hits to putative protease inhibitors. In bovine T.
foetus, CP8 is the preferentially transcribed CP while in the feline
genotype, transcription of CP7 showed higher abundance. In silico
druggability analysis of the two genotypes revealed that when host
sequences are taken into account, drug targets are genotype-specific.
Conclusion: Gene discovery analysis based on RNA-seq data analysis
revealed prominent similarities between the bovine and feline T. foetus, suggesting recent adaptation to their respective host/niche. T. foetus
represents a unique case of a mammalian protozoan expanding its
parasitic grasp across distantly related host lineages. Consequences of
the host-range for in silico drug targeting are exposed here, demonstrating that targets of the parasite in one host are not
necessarily ideal for the same parasite in another host.
extreme organ tropism like the flagellate Tritrichomonas foetus. In
cattle, T. foetus infects the reproductive system causing abortion, whereas the infection in cats results in chronic large bowel diarrhoea.
In the absence of a T. foetus genome, we utilized a de novo approach to
assemble the transcriptome of the bovine and feline genotype to identify
host-specific adaptations and virulence factors specific to each
genotype. Furthermore, a subset of orthologs was used to characterize
putative druggable targets and expose complications of in silico drug
target mining in species with indefinite host-ranges.
Results: Illumina RNA-seq reads were assembled into two representative
bovine and feline transcriptomes containing 42,363 and 36,559 contigs, respectively. Coding and non-coding regions of the genome libraries
revealed striking similarities, with 24,620 shared homolog pairs reduced
down to 7,547 coding orthologs between the two genotypes. The
transcriptomes were near identical in functional category distribution;
with no indication of selective pressure acting on orthologs despite
differences in parasite origins/host. Orthologs formed a large
proportion of highly expressed transcripts in both genotypes (bovine
genotype: 76%, feline genotype: 56%). Mining the libraries for
protease virulence factors revealed the cysteine proteases (CP) to be
the most common. In total, 483 and 445 bovine and feline T. foetus
transcripts were identified as putative proteases based on MEROPS
database, with 9 hits to putative protease inhibitors. In bovine T.
foetus, CP8 is the preferentially transcribed CP while in the feline
genotype, transcription of CP7 showed higher abundance. In silico
druggability analysis of the two genotypes revealed that when host
sequences are taken into account, drug targets are genotype-specific.
Conclusion: Gene discovery analysis based on RNA-seq data analysis
revealed prominent similarities between the bovine and feline T. foetus, suggesting recent adaptation to their respective host/niche. T. foetus
represents a unique case of a mammalian protozoan expanding its
parasitic grasp across distantly related host lineages. Consequences of
the host-range for in silico drug targeting are exposed here, demonstrating that targets of the parasite in one host are not
necessarily ideal for the same parasite in another host.
68.
Sebastian-Leon, P.; Vidal, E.; Minguez, P.; Conesa, A.; Tarazona, S.; Amadoz, A.; Armero, C.; Salavert, F.; Vidal-Puig, A.; Montaner, D.; Dopazo, J.
Understanding disease mechanisms with models of signaling pathway activities Journal Article
In: BMC SYSTEMS BIOLOGY, vol. 8, 2014, ISSN: 1752-0509.
@article{ISI:000347559200001,
title = {Understanding disease mechanisms with models of signaling pathway
activities},
author = { P. Sebastian-Leon and E. Vidal and P. Minguez and A. Conesa and S. Tarazona and A. Amadoz and C. Armero and F. Salavert and A. Vidal-Puig and D. Montaner and J. Dopazo},
url = {http://dx.doi.org/10.1186/s12918-014-0121-3},
doi = {10.1186/s12918-014-0121-3},
issn = {1752-0509},
year = {2014},
date = {2014-10-01},
journal = {BMC SYSTEMS BIOLOGY},
volume = {8},
abstract = {Background: Understanding the aspects of the cell functionality that
account for disease or drug action mechanisms is one of the main
challenges in the analysis of genomic data and is on the basis of the
future implementation of precision medicine.
Results: Here we propose a simple probabilistic model in which signaling
pathways are separated into elementary sub-pathways or signal
transmission circuits (which ultimately trigger cell functions) and then
transforms gene expression measurements into probabilities of activation
of such signal transmission circuits. Using this model, differential
activation of such circuits between biological conditions can be
estimated. Thus, circuit activation statuses can be interpreted as
biomarkers that discriminate among the compared conditions. This type of
mechanism-based biomarkers accounts for cell functional activities and
can easily be associated to disease or drug action mechanisms. The
accuracy of the proposed model is demonstrated with simulations and real
datasets.
Conclusions: The proposed model provides detailed information that
enables the interpretation disease mechanisms as a consequence of the
complex combinations of altered gene expression values. Moreover, it
offers a framework for suggesting possible ways of therapeutic
intervention in a pathologically perturbed system.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Understanding the aspects of the cell functionality that
account for disease or drug action mechanisms is one of the main
challenges in the analysis of genomic data and is on the basis of the
future implementation of precision medicine.
Results: Here we propose a simple probabilistic model in which signaling
pathways are separated into elementary sub-pathways or signal
transmission circuits (which ultimately trigger cell functions) and then
transforms gene expression measurements into probabilities of activation
of such signal transmission circuits. Using this model, differential
activation of such circuits between biological conditions can be
estimated. Thus, circuit activation statuses can be interpreted as
biomarkers that discriminate among the compared conditions. This type of
mechanism-based biomarkers accounts for cell functional activities and
can easily be associated to disease or drug action mechanisms. The
accuracy of the proposed model is demonstrated with simulations and real
datasets.
Conclusions: The proposed model provides detailed information that
enables the interpretation disease mechanisms as a consequence of the
complex combinations of altered gene expression values. Moreover, it
offers a framework for suggesting possible ways of therapeutic
intervention in a pathologically perturbed system.
account for disease or drug action mechanisms is one of the main
challenges in the analysis of genomic data and is on the basis of the
future implementation of precision medicine.
Results: Here we propose a simple probabilistic model in which signaling
pathways are separated into elementary sub-pathways or signal
transmission circuits (which ultimately trigger cell functions) and then
transforms gene expression measurements into probabilities of activation
of such signal transmission circuits. Using this model, differential
activation of such circuits between biological conditions can be
estimated. Thus, circuit activation statuses can be interpreted as
biomarkers that discriminate among the compared conditions. This type of
mechanism-based biomarkers accounts for cell functional activities and
can easily be associated to disease or drug action mechanisms. The
accuracy of the proposed model is demonstrated with simulations and real
datasets.
Conclusions: The proposed model provides detailed information that
enables the interpretation disease mechanisms as a consequence of the
complex combinations of altered gene expression values. Moreover, it
offers a framework for suggesting possible ways of therapeutic
intervention in a pathologically perturbed system.
67.
Su, Z.; Labaj, P. P.; Li, S.; Thierry-Mieg, J.; Thierry-Mieg, D.; Shi, W.; Wang, C.; Schroth, G. P.; Setterquist, R. A.; Thompson, J. F.; Jones, W. D.; Xiao, W.; Xu, W.; Jensen, R. V.; Kelly, R.; Xu, J.; Conesa, A.; Furlanello, C.; Gao, H.; Hong, H.; Jafari, N.; Letovsky, S.; Liao, Y.; Lu, F.; Oakeley, E. J.; Peng, Z.; Praul, C. A.; Santoyo-Lopez, J.; Scherer, A.; Shi, T.; Smyth, G. K.; Staedtler, F.; Sykacek, P.; Tan, X.; Thompson, E. A.; Vandesompele, J.; Wang, M. D.; Wang, J.; Wolfinger, R. D.; Zavadil, J.; Auerbach, S. S.; Bao, W.; Binder, H.; Blomquist, T.; Brilliant, M. H.; Bushel, P. R.; Cain, W.; Catalano, J. G.; Chang, C.; Chen, T.; Chen, G.; Chen, R.; Chierici, M.; Chu, T.; Clevert, D.; Deng, Y.; Derti, A.; Devanarayan, V.; Dong, Z.; Dopazo, J.; Du, T.; Fang, H.; Fang, Y.; Fasold, M.; Fernandez, A.; Fischer, M.; Furio-Tari, P.; Fuscoe, J. C.; Caiment, F.; Gaj, S.; Gandara, J.; Gao, H.; Ge, W.; Gondo, Y.; Gong, B.; Gong, M.; Gong, Z.; Green, B.; Guo, C.; Guo, L.; Guo, L.; Hadfield, J.; Hellemans, J.; Hochreiter, S.; Jia, M.; Jian, M.; Johnson, C. D.; Kay, S.; Kleinjans, J.; Lababidi, S.; Levy, S.; Li, Q.; Li, L.; Li, L.; Li, P.; Li, Y.; Li, H.; Li, J.; Li, S.; Lin, S. M.; Lopez, F. J.; Lu, X.; Luo, H.; Ma, X.; Meehan, J.; Megherbi, D. B.; Mei, N.; Mu, B.; Ning, B.; Pandey, A.; Perez-Florido, J.; Perkins, R. G.; Peters, R.; Phan, J. H.; Pirooznia, M.; Qian, F.; Qing, T.; Rainbow, L.; Rocca-Serra, P.; Sambourg, L.; Sansone, S.; Schwartz, S.; Shah, R.; Shen, J.; Smith, T. M.; Stegle, O.; Stralis-Pavese, N.; Stupka, E.; Suzuki, Y.; Szkotnicki, L. T.; Tinning, M.; Tu, B.; van Deft, J.; Vela-Boza, A.; Venturini, E.; Walker, S. J.; Wan, L.; Wang, W.; Wang, J.; Wang, J.; Wieben, E. D.; Willey, J. C.; Wu, P.; Xuan, J.; Yang, Y.; Ye, Z.; Yin, Y.; Yu, Y.; Yuan, Y.; Zhang, J.; Zhang, K. K.; Zhang, W.; Zhang, W.; Zhang, Y.; Zhao, C.; Zheng, Y.; Zhou, Y.; Zumbo, P.; Tong, W.; Kreil, D. P.; Mason, C. E.; Shi, L.
A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium Journal Article
In: NATURE BIOTECHNOLOGY, vol. 32, no. 9, pp. 903-914, 2014, ISSN: 1087-0156.
@article{ISI:000342600300030,
title = {A comprehensive assessment of RNA-seq accuracy, reproducibility and
information content by the Sequencing Quality Control Consortium},
author = { Z. Su and P. P. Labaj and S. Li and J. Thierry-Mieg and D. Thierry-Mieg and W. Shi and C. Wang and G. P. Schroth and R. A. Setterquist and J. F. Thompson and W. D. Jones and W. Xiao and W. Xu and R. V. Jensen and R. Kelly and J. Xu and A. Conesa and C. Furlanello and H. Gao and H. Hong and N. Jafari and S. Letovsky and Y. Liao and F. Lu and E. J. Oakeley and Z. Peng and C. A. Praul and J. Santoyo-Lopez and A. Scherer and T. Shi and G. K. Smyth and F. Staedtler and P. Sykacek and X. Tan and E. A. Thompson and J. Vandesompele and M. D. Wang and J. Wang and R. D. Wolfinger and J. Zavadil and S. S. Auerbach and W. Bao and H. Binder and T. Blomquist and M. H. Brilliant and P. R. Bushel and W. Cain and J. G. Catalano and C. Chang and T. Chen and G. Chen and R. Chen and M. Chierici and T. Chu and D. Clevert and Y. Deng and A. Derti and V. Devanarayan and Z. Dong and J. Dopazo and T. Du and H. Fang and Y. Fang and M. Fasold and A. Fernandez and M. Fischer and P. Furio-Tari and J. C. Fuscoe and F. Caiment and S. Gaj and J. Gandara and H. Gao and W. Ge and Y. Gondo and B. Gong and M. Gong and Z. Gong and B. Green and C. Guo and L. Guo and L. Guo and J. Hadfield and J. Hellemans and S. Hochreiter and M. Jia and M. Jian and C. D. Johnson and S. Kay and J. Kleinjans and S. Lababidi and S. Levy and Q. Li and L. Li and L. Li and P. Li and Y. Li and H. Li and J. Li and S. Li and S. M. Lin and F. J. Lopez and X. Lu and H. Luo and X. Ma and J. Meehan and D. B. Megherbi and N. Mei and B. Mu and B. Ning and A. Pandey and J. Perez-Florido and R. G. Perkins and R. Peters and J. H. Phan and M. Pirooznia and F. Qian and T. Qing and L. Rainbow and P. Rocca-Serra and L. Sambourg and S. Sansone and S. Schwartz and R. Shah and J. Shen and T. M. Smith and O. Stegle and N. Stralis-Pavese and E. Stupka and Y. Suzuki and L. T. Szkotnicki and M. Tinning and B. Tu and J. van Deft and A. Vela-Boza and E. Venturini and S. J. Walker and L. Wan and W. Wang and J. Wang and J. Wang and E. D. Wieben and J. C. Willey and P. Wu and J. Xuan and Y. Yang and Z. Ye and Y. Yin and Y. Yu and Y. Yuan and J. Zhang and K. K. Zhang and W. Zhang and W. Zhang and Y. Zhang and C. Zhao and Y. Zheng and Y. Zhou and P. Zumbo and W. Tong and D. P. Kreil and C. E. Mason and L. Shi},
url = {http://dx.doi.org/10.1038/nbt.2957},
doi = {10.1038/nbt.2957},
issn = {1087-0156},
year = {2014},
date = {2014-09-01},
journal = {NATURE BIOTECHNOLOGY},
volume = {32},
number = {9},
pages = {903-914},
abstract = {We present primary results from the Sequencing Quality Control (SEQC)
project, coordinated by the US Food and Drug Administration. Examining
Illumina HiSeq, Life Technologies SOLiD and Roche 454 platforms at
multiple laboratory sites using reference RNA samples with built-in
controls, we assess RNA sequencing (RNA-seq) performance for junction
discovery and differential expression profiling and compare it to
microarray and quantitative PCR (qPCR) data using complementary metrics.
At all sequencing depths, we discover unannotated exon-exon junctions, with >80% validated by qPCR. We find that measurements of relative
expression are accurate and reproducible across sites and platforms if
specific-filters are used. In contrast, RNA-seq and microarrays do not
provide accurate absolute measurements, and gene-specific biases are
observed for all examined platforms, including qPCR. Measurement
performance depends on the platform and data analysis pipeline, and
variation is large for transcript-level profiling. The complete SEQC
data sets, comprising >100 billion reads (10Tb), provide unique
resources for evaluating RNA-seq analyses for clinical and regulatory
settings.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We present primary results from the Sequencing Quality Control (SEQC)
project, coordinated by the US Food and Drug Administration. Examining
Illumina HiSeq, Life Technologies SOLiD and Roche 454 platforms at
multiple laboratory sites using reference RNA samples with built-in
controls, we assess RNA sequencing (RNA-seq) performance for junction
discovery and differential expression profiling and compare it to
microarray and quantitative PCR (qPCR) data using complementary metrics.
At all sequencing depths, we discover unannotated exon-exon junctions, with >80% validated by qPCR. We find that measurements of relative
expression are accurate and reproducible across sites and platforms if
specific-filters are used. In contrast, RNA-seq and microarrays do not
provide accurate absolute measurements, and gene-specific biases are
observed for all examined platforms, including qPCR. Measurement
performance depends on the platform and data analysis pipeline, and
variation is large for transcript-level profiling. The complete SEQC
data sets, comprising >100 billion reads (10Tb), provide unique
resources for evaluating RNA-seq analyses for clinical and regulatory
settings.
project, coordinated by the US Food and Drug Administration. Examining
Illumina HiSeq, Life Technologies SOLiD and Roche 454 platforms at
multiple laboratory sites using reference RNA samples with built-in
controls, we assess RNA sequencing (RNA-seq) performance for junction
discovery and differential expression profiling and compare it to
microarray and quantitative PCR (qPCR) data using complementary metrics.
At all sequencing depths, we discover unannotated exon-exon junctions, with >80% validated by qPCR. We find that measurements of relative
expression are accurate and reproducible across sites and platforms if
specific-filters are used. In contrast, RNA-seq and microarrays do not
provide accurate absolute measurements, and gene-specific biases are
observed for all examined platforms, including qPCR. Measurement
performance depends on the platform and data analysis pipeline, and
variation is large for transcript-level profiling. The complete SEQC
data sets, comprising >100 billion reads (10Tb), provide unique
resources for evaluating RNA-seq analyses for clinical and regulatory
settings.
66.
Nueda, M. J.; Tarazona, S.; Conesa, A.
Next maSigPro: updating maSigPro bioconductor package for RNA-seq time series Journal Article
In: BIOINFORMATICS, vol. 30, no. 18, pp. 2598-2602, 2014, ISSN: 1367-4803.
@article{ISI:000342913000008,
title = {Next maSigPro: updating maSigPro bioconductor package for RNA-seq time
series},
author = { M. J. Nueda and S. Tarazona and A. Conesa},
url = {http://dx.doi.org/10.1093/bioinformatics/btu333},
doi = {10.1093/bioinformatics/btu333},
issn = {1367-4803},
year = {2014},
date = {2014-09-01},
journal = {BIOINFORMATICS},
volume = {30},
number = {18},
pages = {2598-2602},
abstract = {Motivation: The widespread adoption of RNA-seq to quantitatively measure
gene expression has increased the scope of sequencing experimental
designs to include time-course experiments. maSigPro is an R package
specifically suited for the analysis of time-course gene expression
data, which was developed originally for microarrays and hence was
limited in its application to count data.
Results: We have updated maSigPro to support RNA-seq time series
analysis by introducing generalized linear models in the algorithm to
support the modeling of count data while maintaining the traditional
functionalities of the package. We show a good performance of the
maSigPro-GLM method in several simulated time-course scenarios and in a
real experimental dataset.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Motivation: The widespread adoption of RNA-seq to quantitatively measure
gene expression has increased the scope of sequencing experimental
designs to include time-course experiments. maSigPro is an R package
specifically suited for the analysis of time-course gene expression
data, which was developed originally for microarrays and hence was
limited in its application to count data.
Results: We have updated maSigPro to support RNA-seq time series
analysis by introducing generalized linear models in the algorithm to
support the modeling of count data while maintaining the traditional
functionalities of the package. We show a good performance of the
maSigPro-GLM method in several simulated time-course scenarios and in a
real experimental dataset.
gene expression has increased the scope of sequencing experimental
designs to include time-course experiments. maSigPro is an R package
specifically suited for the analysis of time-course gene expression
data, which was developed originally for microarrays and hence was
limited in its application to count data.
Results: We have updated maSigPro to support RNA-seq time series
analysis by introducing generalized linear models in the algorithm to
support the modeling of count data while maintaining the traditional
functionalities of the package. We show a good performance of the
maSigPro-GLM method in several simulated time-course scenarios and in a
real experimental dataset.
65.
Munro, S. A.; Lund, S. P.; Pine, P. S.; Binder, H.; Clevert, D.; Conesa, A.; Dopazo, J.; Fasold, M.; Hochreiter, S.; Hong, H.; Jafari, N.; Kreil, D. P.; Labaj, P. P.; Li, S.; Liao, Y.; Lin, S. M.; Meehan, J.; Mason, C. E.; Santoyo-Lopez, J.; Setterquist, R. A.; Shi, L.; Shi, W.; Smyth, G. K.; Stralis-Pavese, N.; Su, Z.; Tong, W.; Wang, C.; Wang, J.; Xu, J.; Ye, Z.; Yang, Y.; Yu, Y.; Salit, M.
Assessing technical performance in differential gene expression experiments with external spike-in RNA control ratio mixtures Journal Article
In: NATURE COMMUNICATIONS, vol. 5, 2014, ISSN: 2041-1723.
@article{ISI:000343030500001,
title = {Assessing technical performance in differential gene expression
experiments with external spike-in RNA control ratio mixtures},
author = { S. A. Munro and S. P. Lund and P. S. Pine and H. Binder and D. Clevert and A. Conesa and J. Dopazo and M. Fasold and S. Hochreiter and H. Hong and N. Jafari and D. P. Kreil and P. P. Labaj and S. Li and Y. Liao and S. M. Lin and J. Meehan and C. E. Mason and J. Santoyo-Lopez and R. A. Setterquist and L. Shi and W. Shi and G. K. Smyth and N. Stralis-Pavese and Z. Su and W. Tong and C. Wang and J. Wang and J. Xu and Z. Ye and Y. Yang and Y. Yu and M. Salit},
url = {http://dx.doi.org/10.1038/ncomms6125},
doi = {10.1038/ncomms6125},
issn = {2041-1723},
year = {2014},
date = {2014-09-01},
journal = {NATURE COMMUNICATIONS},
volume = {5},
abstract = {There is a critical need for standard approaches to assess, report and
compare the technical performance of genome-scale differential gene
expression experiments. Here we assess technical performance with a
proposed standard `dashboard' of metrics derived from analysis of
external spike-in RNA control ratio mixtures. These control ratio
mixtures with defined abundance ratios enable assessment of diagnostic
performance of differentially expressed transcript lists, limit of
detection of ratio (LODR) estimates and expression ratio variability and
measurement bias. The performance metrics suite is applicable to
analysis of a typical experiment, and here we also apply these metrics
to evaluate technical performance among laboratories. An interlaboratory
study using identical samples shared among 12 laboratories with three
different measurement processes demonstrates generally consistent
diagnostic power across 11 laboratories. Ratio measurement variability
and bias are also comparable among laboratories for the same measurement
process. We observe different biases for measurement processes using
different mRNA-enrichment protocols.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
There is a critical need for standard approaches to assess, report and
compare the technical performance of genome-scale differential gene
expression experiments. Here we assess technical performance with a
proposed standard `dashboard' of metrics derived from analysis of
external spike-in RNA control ratio mixtures. These control ratio
mixtures with defined abundance ratios enable assessment of diagnostic
performance of differentially expressed transcript lists, limit of
detection of ratio (LODR) estimates and expression ratio variability and
measurement bias. The performance metrics suite is applicable to
analysis of a typical experiment, and here we also apply these metrics
to evaluate technical performance among laboratories. An interlaboratory
study using identical samples shared among 12 laboratories with three
different measurement processes demonstrates generally consistent
diagnostic power across 11 laboratories. Ratio measurement variability
and bias are also comparable among laboratories for the same measurement
process. We observe different biases for measurement processes using
different mRNA-enrichment protocols.
compare the technical performance of genome-scale differential gene
expression experiments. Here we assess technical performance with a
proposed standard `dashboard' of metrics derived from analysis of
external spike-in RNA control ratio mixtures. These control ratio
mixtures with defined abundance ratios enable assessment of diagnostic
performance of differentially expressed transcript lists, limit of
detection of ratio (LODR) estimates and expression ratio variability and
measurement bias. The performance metrics suite is applicable to
analysis of a typical experiment, and here we also apply these metrics
to evaluate technical performance among laboratories. An interlaboratory
study using identical samples shared among 12 laboratories with three
different measurement processes demonstrates generally consistent
diagnostic power across 11 laboratories. Ratio measurement variability
and bias are also comparable among laboratories for the same measurement
process. We observe different biases for measurement processes using
different mRNA-enrichment protocols.
64.
Sevilla, M. Turpin; Carbonell-Munoz, R.; Garcia-Solano, J.; Torres-Moreno, D.; Garcia-Garcia, F.; Conesa, A.; Perez-Guillermo, M.; Conesa-Zamora, P.
Differentially expressed functions and genes between serrated adenocarcinoma and sporadic colorectal carcinoma showing histological and molecular features of high level of microsatellite instability Journal Article
In: EUROPEAN JOURNAL OF CANCER, vol. 50, no. 5, pp. S219, 2014, ISSN: 0959-8049.
@article{ISI:000351589702079,
title = {Differentially expressed functions and genes between serrated
adenocarcinoma and sporadic colorectal carcinoma showing histological
and molecular features of high level of microsatellite instability},
author = { M. Turpin Sevilla and R. Carbonell-Munoz and J. Garcia-Solano and D. Torres-Moreno and F. Garcia-Garcia and A. Conesa and M. Perez-Guillermo and P. Conesa-Zamora},
issn = {0959-8049},
year = {2014},
date = {2014-07-01},
journal = {EUROPEAN JOURNAL OF CANCER},
volume = {50},
number = {5},
pages = {S219},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
63.
Almouzni, G.; Altucci, L.; Amati, B.; Ashley, N.; Baulcombe, D.; Beaujean, N.; Bock, C.; Bongcam-Rudloff, E.; Bousquet, J.; Braun, S.; Paillerets, B. Bressac-de; Bussemakers, M.; Clarke, L.; Conesa, A.; Estivill, X.; Fazeli, A.; Grgurevic, N.; Gut, I.; Heijmans, B. T.; Hermouet, S.; Houwing-Duistermaat, J.; Iacobucci, I.; Ilas, J.; Kandimalla, R.; Krauss-Etschmann, S.; Lasko, P.; Lehmann, S.; Lindroth, A.; Majdic, G.; Marcotte, E.; Martinelli, G.; Martinet, N.; Meyer, E.; Miceli, C.; Mills, K.; Moreno-Villanueva, M.; Morvan, G.; Nickel, D.; Niesler, B.; Nowacki, M.; Nowak, J.; Ossowski, S.; Pelizzola, M.; Pochet, R.; Potocnik, U.; Radwanska, M.; Raes, J.; Rattray, M.; Robinson, M. D.; Roelen, B.; Sauer, S.; Schinzer, D.; Slagboom, E.; Spector, T.; Stunnenberg, H. G.; Tiligada, E.; Torres-Padilla, M.; Tsonaka, R.; Soom, A. Van; Vidakovic, M.; Widschwendter, M.
Relationship between genome and epigenome - challenges and requirements for future research Journal Article
In: BMC GENOMICS, vol. 15, 2014, ISSN: 1471-2164.
@article{ISI:000338246200001,
title = {Relationship between genome and epigenome - challenges and requirements
for future research},
author = { G. Almouzni and L. Altucci and B. Amati and N. Ashley and D. Baulcombe and N. Beaujean and C. Bock and E. Bongcam-Rudloff and J. Bousquet and S. Braun and B. Bressac-de Paillerets and M. Bussemakers and L. Clarke and A. Conesa and X. Estivill and A. Fazeli and N. Grgurevic and I. Gut and B. T. Heijmans and S. Hermouet and J. Houwing-Duistermaat and I. Iacobucci and J. Ilas and R. Kandimalla and S. Krauss-Etschmann and P. Lasko and S. Lehmann and A. Lindroth and G. Majdic and E. Marcotte and G. Martinelli and N. Martinet and E. Meyer and C. Miceli and K. Mills and M. Moreno-Villanueva and G. Morvan and D. Nickel and B. Niesler and M. Nowacki and J. Nowak and S. Ossowski and M. Pelizzola and R. Pochet and U. Potocnik and M. Radwanska and J. Raes and M. Rattray and M. D. Robinson and B. Roelen and S. Sauer and D. Schinzer and E. Slagboom and T. Spector and H. G. Stunnenberg and E. Tiligada and M. Torres-Padilla and R. Tsonaka and A. Van Soom and M. Vidakovic and M. Widschwendter},
url = {http://dx.doi.org/10.1186/1471-2164-15-487},
doi = {10.1186/1471-2164-15-487},
issn = {1471-2164},
year = {2014},
date = {2014-06-01},
journal = {BMC GENOMICS},
volume = {15},
abstract = {Understanding the links between genetic, epigenetic and non-genetic
factors throughout the lifespan and across generations and their role in
disease susceptibility and disease progression offer entirely new
avenues and solutions to major problems in our society. To overcome the
numerous challenges, we have come up with nine major conclusions to set
the vision for future policies and research agendas at the European
level.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Understanding the links between genetic, epigenetic and non-genetic
factors throughout the lifespan and across generations and their role in
disease susceptibility and disease progression offer entirely new
avenues and solutions to major problems in our society. To overcome the
numerous challenges, we have come up with nine major conclusions to set
the vision for future policies and research agendas at the European
level.
factors throughout the lifespan and across generations and their role in
disease susceptibility and disease progression offer entirely new
avenues and solutions to major problems in our society. To overcome the
numerous challenges, we have come up with nine major conclusions to set
the vision for future policies and research agendas at the European
level.
62.
Larriba, E.; Jaime, M. D. L. A.; Carbonell-Caballero, J.; Conesa, A.; Dopazo, J.; Nislow, C.; Martin-Nieto, J.; Lopez-Llorca, L. Vicente
Sequencing and functional analysis of the genome of a nematode egg-parasitic fungus, Pochonia chlamydosporia Journal Article
In: FUNGAL GENETICS AND BIOLOGY, vol. 65, pp. 69-80, 2014, ISSN: 1087-1845.
@article{ISI:000333499100007,
title = {Sequencing and functional analysis of the genome of a nematode
egg-parasitic fungus, Pochonia chlamydosporia},
author = { E. Larriba and M. D. L. A. Jaime and J. Carbonell-Caballero and A. Conesa and J. Dopazo and C. Nislow and J. Martin-Nieto and L. Vicente Lopez-Llorca},
url = {http://dx.doi.org/10.1016/j.fgb.2014.02.002},
doi = {10.1016/j.fgb.2014.02.002},
issn = {1087-1845},
year = {2014},
date = {2014-04-01},
journal = {FUNGAL GENETICS AND BIOLOGY},
volume = {65},
pages = {69-80},
abstract = {Pochonia chlamydosporia is a worldwide-distributed soil fungus with a
great capacity to infect and destroy the eggs and kill females of
plant-parasitic nematodes. Additionally, it has the ability to colonize
endophytically roots of economically-important crop plants, thereby
promoting their growth and eliciting plant defenses. This multitrophic
behavior makes P. chlamydosporia a potentially useful tool for
sustainable agriculture approaches. We sequenced and assembled similar
to 41 Mb of P. chlamydosporia genomic DNA and predicted 12,122 gene
models, of which many were homologous to genes of fungal pathogens of
invertebrates and fungal plant pathogens. Predicted genes (65%) were
functionally annotated according to Gene Ontology, and 16% of them
found to share homology with genes in the Pathogen Host Interactions
(PHI) database. The genome of this fungus is highly enriched in genes
encoding hydrolytic enzymes, such as proteases, glycoside hydrolases and
carbohydrate esterases. We used RNA-Seq technology in order to identify
the genes expressed during endophytic behavior of P. chlamydosporia when
colonizing barley roots. Functional annotation of these genes showed
that hydrolytic enzymes and transporters are expressed during
endophytism. This structural and functional analysis of the P.
chlamydosporia genome provides a starting point for understanding the
molecular mechanisms involved in the multitrophic lifestyle of this
fungus. The genomic information provided here should also prove useful
for enhancing the capabilities of this fungus as a biocontrol agent of
plant-parasitic nematodes and as a plant growth-promoting organism. (C)
2014 Elsevier Inc. All rights reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Pochonia chlamydosporia is a worldwide-distributed soil fungus with a
great capacity to infect and destroy the eggs and kill females of
plant-parasitic nematodes. Additionally, it has the ability to colonize
endophytically roots of economically-important crop plants, thereby
promoting their growth and eliciting plant defenses. This multitrophic
behavior makes P. chlamydosporia a potentially useful tool for
sustainable agriculture approaches. We sequenced and assembled similar
to 41 Mb of P. chlamydosporia genomic DNA and predicted 12,122 gene
models, of which many were homologous to genes of fungal pathogens of
invertebrates and fungal plant pathogens. Predicted genes (65%) were
functionally annotated according to Gene Ontology, and 16% of them
found to share homology with genes in the Pathogen Host Interactions
(PHI) database. The genome of this fungus is highly enriched in genes
encoding hydrolytic enzymes, such as proteases, glycoside hydrolases and
carbohydrate esterases. We used RNA-Seq technology in order to identify
the genes expressed during endophytic behavior of P. chlamydosporia when
colonizing barley roots. Functional annotation of these genes showed
that hydrolytic enzymes and transporters are expressed during
endophytism. This structural and functional analysis of the P.
chlamydosporia genome provides a starting point for understanding the
molecular mechanisms involved in the multitrophic lifestyle of this
fungus. The genomic information provided here should also prove useful
for enhancing the capabilities of this fungus as a biocontrol agent of
plant-parasitic nematodes and as a plant growth-promoting organism. (C)
2014 Elsevier Inc. All rights reserved.
great capacity to infect and destroy the eggs and kill females of
plant-parasitic nematodes. Additionally, it has the ability to colonize
endophytically roots of economically-important crop plants, thereby
promoting their growth and eliciting plant defenses. This multitrophic
behavior makes P. chlamydosporia a potentially useful tool for
sustainable agriculture approaches. We sequenced and assembled similar
to 41 Mb of P. chlamydosporia genomic DNA and predicted 12,122 gene
models, of which many were homologous to genes of fungal pathogens of
invertebrates and fungal plant pathogens. Predicted genes (65%) were
functionally annotated according to Gene Ontology, and 16% of them
found to share homology with genes in the Pathogen Host Interactions
(PHI) database. The genome of this fungus is highly enriched in genes
encoding hydrolytic enzymes, such as proteases, glycoside hydrolases and
carbohydrate esterases. We used RNA-Seq technology in order to identify
the genes expressed during endophytic behavior of P. chlamydosporia when
colonizing barley roots. Functional annotation of these genes showed
that hydrolytic enzymes and transporters are expressed during
endophytism. This structural and functional analysis of the P.
chlamydosporia genome provides a starting point for understanding the
molecular mechanisms involved in the multitrophic lifestyle of this
fungus. The genomic information provided here should also prove useful
for enhancing the capabilities of this fungus as a biocontrol agent of
plant-parasitic nematodes and as a plant growth-promoting organism. (C)
2014 Elsevier Inc. All rights reserved.
61.
Desoignies, N.; Carbonell, J.; Moreau, J. -S.; Conesa, A.; Dopazo, J.; Legreve, A.
Molecular interactions between sugar beet and Polymyxa betae during its life cycle Journal Article
In: ANNALS OF APPLIED BIOLOGY, vol. 164, no. 2, pp. 244-256, 2014, ISSN: 0003-4746.
@article{ISI:000331407000009,
title = {Molecular interactions between sugar beet and Polymyxa betae during its
life cycle},
author = { N. Desoignies and J. Carbonell and J. -S. Moreau and A. Conesa and J. Dopazo and A. Legreve},
url = {http://dx.doi.org/10.1111/aab.12095},
doi = {10.1111/aab.12095},
issn = {0003-4746},
year = {2014},
date = {2014-03-01},
journal = {ANNALS OF APPLIED BIOLOGY},
volume = {164},
number = {2},
pages = {244-256},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
60.
Gomez-Cabrero, D.; Abugessaisa, I.; Maier, D.; Teschendorff, A.; Merkenschlager, M.; Gisel, A.; Ballestar, E.; Bongcam-Rudloff, E.; Conesa, A.; Tegner, J.
Data integration in the era of omics: current and future challenges Journal Article
In: BMC SYSTEMS BIOLOGY, vol. 8, no. 2, 2014, ISSN: 1752-0509.
@article{ISI:000333681300001,
title = {Data integration in the era of omics: current and future challenges},
author = { D. Gomez-Cabrero and I. Abugessaisa and D. Maier and A. Teschendorff and M. Merkenschlager and A. Gisel and E. Ballestar and E. Bongcam-Rudloff and A. Conesa and J. Tegner},
url = {http://dx.doi.org/10.1186/1752-0509-8-S2-I1},
doi = {10.1186/1752-0509-8-S2-I1},
issn = {1752-0509},
year = {2014},
date = {2014-03-01},
journal = {BMC SYSTEMS BIOLOGY},
volume = {8},
number = {2},
abstract = {To integrate heterogeneous and large omics data constitutes not only a
conceptual challenge but a practical hurdle in the daily analysis of
omics data. With the rise of novel omics technologies and through
large-scale consortia projects, biological systems are being further
investigated at an unprecedented scale generating heterogeneous and
often large data sets. These data-sets encourage researchers to develop
novel data integration methodologies. In this introduction we review the
definition and characterize current efforts on data integration in the
life sciences. We have used a web-survey to assess current research
projects on data-integration to tap into the views, needs and challenges
as currently perceived by parts of the research community.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
To integrate heterogeneous and large omics data constitutes not only a
conceptual challenge but a practical hurdle in the daily analysis of
omics data. With the rise of novel omics technologies and through
large-scale consortia projects, biological systems are being further
investigated at an unprecedented scale generating heterogeneous and
often large data sets. These data-sets encourage researchers to develop
novel data integration methodologies. In this introduction we review the
definition and characterize current efforts on data integration in the
life sciences. We have used a web-survey to assess current research
projects on data-integration to tap into the views, needs and challenges
as currently perceived by parts of the research community.
conceptual challenge but a practical hurdle in the daily analysis of
omics data. With the rise of novel omics technologies and through
large-scale consortia projects, biological systems are being further
investigated at an unprecedented scale generating heterogeneous and
often large data sets. These data-sets encourage researchers to develop
novel data integration methodologies. In this introduction we review the
definition and characterize current efforts on data integration in the
life sciences. We have used a web-survey to assess current research
projects on data-integration to tap into the views, needs and challenges
as currently perceived by parts of the research community.
59.
Conesa, A.; Mortazavi, A.
The common ground of genomics and systems biology Journal Article
In: BMC SYSTEMS BIOLOGY, vol. 8, no. 2, 2014, ISSN: 1752-0509, (High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013).
@article{ISI:000333681300002,
title = {The common ground of genomics and systems biology},
author = { A. Conesa and A. Mortazavi},
url = {http://dx.doi.org/10.1186/1752-0509-8-S2-S1},
doi = {10.1186/1752-0509-8-S2-S1},
issn = {1752-0509},
year = {2014},
date = {2014-03-01},
journal = {BMC SYSTEMS BIOLOGY},
volume = {8},
number = {2},
abstract = {The rise of systems biology is intertwined with that of genomics, yet
their primordial relationship to one another is ill-defined. We discuss
how the growth of genomics provided a critical boost to the popularity
of systems biology. We describe the parts of genomics that share common
areas of interest with systems biology today in the areas of gene
expression, network inference, chromatin state analysis, pathway
analysis, personalized medicine, and upcoming areas of synergy as
genomics continues to expand its scope across all biomedical fields.},
note = {High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The rise of systems biology is intertwined with that of genomics, yet
their primordial relationship to one another is ill-defined. We discuss
how the growth of genomics provided a critical boost to the popularity
of systems biology. We describe the parts of genomics that share common
areas of interest with systems biology today in the areas of gene
expression, network inference, chromatin state analysis, pathway
analysis, personalized medicine, and upcoming areas of synergy as
genomics continues to expand its scope across all biomedical fields.
their primordial relationship to one another is ill-defined. We discuss
how the growth of genomics provided a critical boost to the popularity
of systems biology. We describe the parts of genomics that share common
areas of interest with systems biology today in the areas of gene
expression, network inference, chromatin state analysis, pathway
analysis, personalized medicine, and upcoming areas of synergy as
genomics continues to expand its scope across all biomedical fields.
58.
Ponzoni, I.; Nueda, M. J.; Tarazona, S.; Goetz, S.; Montaner, D.; Dussaut, J. S.; Dopazo, J.; Conesa, A.
Pathway network inference from gene expression data Journal Article
In: BMC SYSTEMS BIOLOGY, vol. 8, no. 2, 2014, ISSN: 1752-0509, (High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013).
@article{ISI:000333681300008,
title = {Pathway network inference from gene expression data},
author = { I. Ponzoni and M. J. Nueda and S. Tarazona and S. Goetz and D. Montaner and J. S. Dussaut and J. Dopazo and A. Conesa},
url = {http://dx.doi.org/10.1186/1752-0509-8-S2-S7},
doi = {10.1186/1752-0509-8-S2-S7},
issn = {1752-0509},
year = {2014},
date = {2014-03-01},
journal = {BMC SYSTEMS BIOLOGY},
volume = {8},
number = {2},
abstract = {Background: The development of high-throughput omics technologies
enabled genome-wide measurements of the activity of cellular elements
and provides the analytical resources for the progress of the Systems
Biology discipline. Analysis and interpretation of gene expression data
has evolved from the gene to the pathway and interaction level, i.e.
from the detection of differentially expressed genes, to the
establishment of gene interaction networks and the identification of
enriched functional categories. Still, the understanding of biological
systems requires a further level of analysis that addresses the
characterization of the interaction between functional modules.
Results: We present a novel computational methodology to study the
functional interconnections among the molecular elements of a biological
system. The PANA approach uses high-throughput genomics measurements and
a functional annotation scheme to extract an activity profile from each
functional block -or pathway-followed by machine-learning methods to
infer the relationships between these functional profiles. The result is
a global, interconnected network of pathways that represents the
functional cross-talk within the molecular system. We have applied this
approach to describe the functional transcriptional connections during
the yeast cell cycle and to identify pathways that change their
connectivity in a disease condition using an Alzheimer example.
Conclusions: PANA is a useful tool to deepen in our understanding of the
functional interdependences that operate within complex biological
systems. We show the approach is algorithmically consistent and the
inferred network is well supported by the available functional data. The
method allows the dissection of the molecular basis of the functional
connections and we describe the different regulatory mechanisms that
explain the network's topology obtained for the yeast cell cycle data.},
note = {High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: The development of high-throughput omics technologies
enabled genome-wide measurements of the activity of cellular elements
and provides the analytical resources for the progress of the Systems
Biology discipline. Analysis and interpretation of gene expression data
has evolved from the gene to the pathway and interaction level, i.e.
from the detection of differentially expressed genes, to the
establishment of gene interaction networks and the identification of
enriched functional categories. Still, the understanding of biological
systems requires a further level of analysis that addresses the
characterization of the interaction between functional modules.
Results: We present a novel computational methodology to study the
functional interconnections among the molecular elements of a biological
system. The PANA approach uses high-throughput genomics measurements and
a functional annotation scheme to extract an activity profile from each
functional block -or pathway-followed by machine-learning methods to
infer the relationships between these functional profiles. The result is
a global, interconnected network of pathways that represents the
functional cross-talk within the molecular system. We have applied this
approach to describe the functional transcriptional connections during
the yeast cell cycle and to identify pathways that change their
connectivity in a disease condition using an Alzheimer example.
Conclusions: PANA is a useful tool to deepen in our understanding of the
functional interdependences that operate within complex biological
systems. We show the approach is algorithmically consistent and the
inferred network is well supported by the available functional data. The
method allows the dissection of the molecular basis of the functional
connections and we describe the different regulatory mechanisms that
explain the network's topology obtained for the yeast cell cycle data.
enabled genome-wide measurements of the activity of cellular elements
and provides the analytical resources for the progress of the Systems
Biology discipline. Analysis and interpretation of gene expression data
has evolved from the gene to the pathway and interaction level, i.e.
from the detection of differentially expressed genes, to the
establishment of gene interaction networks and the identification of
enriched functional categories. Still, the understanding of biological
systems requires a further level of analysis that addresses the
characterization of the interaction between functional modules.
Results: We present a novel computational methodology to study the
functional interconnections among the molecular elements of a biological
system. The PANA approach uses high-throughput genomics measurements and
a functional annotation scheme to extract an activity profile from each
functional block -or pathway-followed by machine-learning methods to
infer the relationships between these functional profiles. The result is
a global, interconnected network of pathways that represents the
functional cross-talk within the molecular system. We have applied this
approach to describe the functional transcriptional connections during
the yeast cell cycle and to identify pathways that change their
connectivity in a disease condition using an Alzheimer example.
Conclusions: PANA is a useful tool to deepen in our understanding of the
functional interdependences that operate within complex biological
systems. We show the approach is algorithmically consistent and the
inferred network is well supported by the available functional data. The
method allows the dissection of the molecular basis of the functional
connections and we describe the different regulatory mechanisms that
explain the network's topology obtained for the yeast cell cycle data.
57.
de Diego, R. Hernandez; Boix-Chova, N.; Gomez-Cabrero, D.; Tegner, J.; Abugessaisa, I.; Conesa, A.
STATegra EMS: an Experiment Management System for complex next-generation omics experiments Journal Article
In: BMC SYSTEMS BIOLOGY, vol. 8, no. 2, 2014, ISSN: 1752-0509, (High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013).
@article{ISI:000333681300010,
title = {STATegra EMS: an Experiment Management System for complex
next-generation omics experiments},
author = { R. Hernandez de Diego and N. Boix-Chova and D. Gomez-Cabrero and J. Tegner and I. Abugessaisa and A. Conesa},
url = {http://dx.doi.org/10.1186/1752-0509-8-S2-S9},
doi = {10.1186/1752-0509-8-S2-S9},
issn = {1752-0509},
year = {2014},
date = {2014-03-01},
journal = {BMC SYSTEMS BIOLOGY},
volume = {8},
number = {2},
abstract = {High-throughput sequencing assays are now routinely used to study
different aspects of genome organization. As decreasing costs and
widespread availability of sequencing enable more laboratories to use
sequencing assays in their research projects, the number of samples and
replicates in these experiments can quickly grow to several dozens of
samples and thus require standardized annotation, storage and management
of preprocessing steps. As a part of the STATegra project, we have
developed an Experiment Management System (EMS) for high throughput
omics data that supports different types of sequencing-based assays such
as RNA-seq, ChIP-seq, Methyl-seq, etc, as well as proteomics and
metabolomics data. The STATegra EMS provides metadata annotation of
experimental design, samples and processing pipelines, as well as
storage of different types of data files, from raw data to ready-to-use
measurements. The system has been developed to provide research
laboratories with a freely-available, integrated system that offers a
simple and effective way for experiment annotation and tracking of
analysis procedures.},
note = {High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
High-throughput sequencing assays are now routinely used to study
different aspects of genome organization. As decreasing costs and
widespread availability of sequencing enable more laboratories to use
sequencing assays in their research projects, the number of samples and
replicates in these experiments can quickly grow to several dozens of
samples and thus require standardized annotation, storage and management
of preprocessing steps. As a part of the STATegra project, we have
developed an Experiment Management System (EMS) for high throughput
omics data that supports different types of sequencing-based assays such
as RNA-seq, ChIP-seq, Methyl-seq, etc, as well as proteomics and
metabolomics data. The STATegra EMS provides metadata annotation of
experimental design, samples and processing pipelines, as well as
storage of different types of data files, from raw data to ready-to-use
measurements. The system has been developed to provide research
laboratories with a freely-available, integrated system that offers a
simple and effective way for experiment annotation and tracking of
analysis procedures.
different aspects of genome organization. As decreasing costs and
widespread availability of sequencing enable more laboratories to use
sequencing assays in their research projects, the number of samples and
replicates in these experiments can quickly grow to several dozens of
samples and thus require standardized annotation, storage and management
of preprocessing steps. As a part of the STATegra project, we have
developed an Experiment Management System (EMS) for high throughput
omics data that supports different types of sequencing-based assays such
as RNA-seq, ChIP-seq, Methyl-seq, etc, as well as proteomics and
metabolomics data. The STATegra EMS provides metadata annotation of
experimental design, samples and processing pipelines, as well as
storage of different types of data files, from raw data to ready-to-use
measurements. The system has been developed to provide research
laboratories with a freely-available, integrated system that offers a
simple and effective way for experiment annotation and tracking of
analysis procedures.
56.
Garcia-Solano, J.; Alcaraz-Mateos, E.; Wilce, J.; Torres-Moreno, D.; Turpin-Sevilla, M. C.; Navarre, C.; Conesa, A.; Tuomisto, A.; Sirnio, P.; Makinen, M. J.; Perez-Guillermo, M.; Conesa-Zamora, P.
Methylation Microarray Analysis Identifies Differentially Methylated Genes in Serrated Compared to Conventional Colorectal Carcinomas Journal Article
In: LABORATORY INVESTIGATION, vol. 94, no. 1, pp. 174A, 2014, ISSN: 0023-6837, (103rd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP), San Diego, CA, MAR 01-07, 2014).
@article{ISI:000331155800710,
title = {Methylation Microarray Analysis Identifies Differentially Methylated
Genes in Serrated Compared to Conventional Colorectal Carcinomas},
author = { J. Garcia-Solano and E. Alcaraz-Mateos and J. Wilce and D. Torres-Moreno and M. C. Turpin-Sevilla and C. Navarre and A. Conesa and A. Tuomisto and P. Sirnio and M. J. Makinen and M. Perez-Guillermo and P. Conesa-Zamora},
issn = {0023-6837},
year = {2014},
date = {2014-02-01},
journal = {LABORATORY INVESTIGATION},
volume = {94},
number = {1},
pages = {174A},
organization = {US & Canadian Acad Pathol; Dako; Biocare Med; Leica Biosystems; LabCorp
Specialty Testing Grp, Integrated Oncol; GenomOncology; Nephropath;
Ventana; Diagnost BioSystems},
note = {103rd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP), San Diego, CA, MAR 01-07, 2014},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
55.
Garica-Solano, J.; Alcaraz-Mateos, E.; Wilce, J.; Torres-Moreno, D.; Turpin-Sevilla, M. C.; Navarre, C.; Conesa, A.; Tuomisto, A.; Sirnio, P.; Makinen, M. J.; Perez-Guillermo, M.; Conesa-Zamora, P.
Methylation Microarray Analysis Identifies Differentially Methylated Genes in Serrated Compared to Conventional Colorectal Carcinomas Journal Article
In: MODERN PATHOLOGY, vol. 27, no. 2, pp. 174A, 2014, ISSN: 0893-3952, (103rd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP), San Diego, CA, MAR 01-07, 2014).
@article{ISI:000331502201024,
title = {Methylation Microarray Analysis Identifies Differentially Methylated
Genes in Serrated Compared to Conventional Colorectal Carcinomas},
author = { J. Garica-Solano and E. Alcaraz-Mateos and J. Wilce and D. Torres-Moreno and M. C. Turpin-Sevilla and C. Navarre and A. Conesa and A. Tuomisto and P. Sirnio and M. J. Makinen and M. Perez-Guillermo and P. Conesa-Zamora},
issn = {0893-3952},
year = {2014},
date = {2014-02-01},
journal = {MODERN PATHOLOGY},
volume = {27},
number = {2},
pages = {174A},
organization = {US & Canadian Acad Pathol; Dako; Biocare Med; Leica Biosystems; LabCorp
Specialty Testing Grp, Integrated Oncol; GenomOncology; Nephropath;
Ventana; Diagnost BioSystems},
note = {103rd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP), San Diego, CA, MAR 01-07, 2014},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2013
54.
Galan, A.; Diaz-Gimeno, P.; Poo, M. Eugenia; Valbuena, D.; Sanchez, E.; Ruiz, V.; Dopazo, J.; Montaner, D.; Conesa, A.; Simon, C.
Defining the Genomic Signature of Totipotency and Pluripotency during Early Human Development Journal Article
In: PLOS ONE, vol. 8, no. 4, 2013, ISSN: 1932-6203.
@article{ISI:000317907200122,
title = {Defining the Genomic Signature of Totipotency and Pluripotency during
Early Human Development},
author = { A. Galan and P. Diaz-Gimeno and M. Eugenia Poo and D. Valbuena and E. Sanchez and V. Ruiz and J. Dopazo and D. Montaner and A. Conesa and C. Simon},
url = {http://dx.doi.org/10.1371/journal.pone.0062135},
doi = {10.1371/journal.pone.0062135},
issn = {1932-6203},
year = {2013},
date = {2013-04-01},
journal = {PLOS ONE},
volume = {8},
number = {4},
abstract = {The genetic mechanisms governing human pre-implantation embryo
development and the in vitro counterparts, human embryonic stem cells
(hESCs), still remain incomplete. Previous global genome studies
demonstrated that totipotent blastomeres from day-3 human embryos and
pluripotent inner cell masses (ICMs) from blastocysts, display unique
and differing transcriptomes. Nevertheless, comparative gene expression
analysis has revealed that no significant differences exist between
hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental
progression. To understand early human stages evolution, we developed an
undifferentiation network signature (UNS) and applied it to a
differential gene expression profile between single blastomeres from
day-3 embryos, ICMs and hESCs. This allowed us to establish a unique
signature composed of highly interconnected genes characteristic of
totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro
pluripotency (107 genes), and which are also proprietary according to
functional analysis. This systems biology approach has led to an
improved understanding of the molecular and signaling processes
governing human pre-implantation embryo development, as well as enabling
us to comprehend how hESCs might adapt to in vitro culture conditions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The genetic mechanisms governing human pre-implantation embryo
development and the in vitro counterparts, human embryonic stem cells
(hESCs), still remain incomplete. Previous global genome studies
demonstrated that totipotent blastomeres from day-3 human embryos and
pluripotent inner cell masses (ICMs) from blastocysts, display unique
and differing transcriptomes. Nevertheless, comparative gene expression
analysis has revealed that no significant differences exist between
hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental
progression. To understand early human stages evolution, we developed an
undifferentiation network signature (UNS) and applied it to a
differential gene expression profile between single blastomeres from
day-3 embryos, ICMs and hESCs. This allowed us to establish a unique
signature composed of highly interconnected genes characteristic of
totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro
pluripotency (107 genes), and which are also proprietary according to
functional analysis. This systems biology approach has led to an
improved understanding of the molecular and signaling processes
governing human pre-implantation embryo development, as well as enabling
us to comprehend how hESCs might adapt to in vitro culture conditions.
development and the in vitro counterparts, human embryonic stem cells
(hESCs), still remain incomplete. Previous global genome studies
demonstrated that totipotent blastomeres from day-3 human embryos and
pluripotent inner cell masses (ICMs) from blastocysts, display unique
and differing transcriptomes. Nevertheless, comparative gene expression
analysis has revealed that no significant differences exist between
hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental
progression. To understand early human stages evolution, we developed an
undifferentiation network signature (UNS) and applied it to a
differential gene expression profile between single blastomeres from
day-3 embryos, ICMs and hESCs. This allowed us to establish a unique
signature composed of highly interconnected genes characteristic of
totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro
pluripotency (107 genes), and which are also proprietary according to
functional analysis. This systems biology approach has led to an
improved understanding of the molecular and signaling processes
governing human pre-implantation embryo development, as well as enabling
us to comprehend how hESCs might adapt to in vitro culture conditions.
53.
Conesa-Zamora, P.; Garcia-Solano, J.; Garcia-Garcia, F.; del Carmen Turpin, M.; Trujillo-Santos, J.; Torres-Moreno, D.; Oviedo-Ramirez, I.; Carbonell-Munoz, R.; Munoz-Delgado, E.; Rodriguez-Braun, E.; Conesa, A.; Perez-Guillermo, M.
In: INTERNATIONAL JOURNAL OF CANCER, vol. 132, no. 2, pp. 297-307, 2013, ISSN: 0020-7136.
@article{ISI:000311383600015,
title = {Expression profiling shows differential molecular pathways and provides
potential new diagnostic biomarkers for colorectal serrated
adenocarcinoma},
author = { P. Conesa-Zamora and J. Garcia-Solano and F. Garcia-Garcia and M. del Carmen Turpin and J. Trujillo-Santos and D. Torres-Moreno and I. Oviedo-Ramirez and R. Carbonell-Munoz and E. Munoz-Delgado and E. Rodriguez-Braun and A. Conesa and M. Perez-Guillermo},
url = {http://dx.doi.org/10.1002/ijc.27674},
doi = {10.1002/ijc.27674},
issn = {0020-7136},
year = {2013},
date = {2013-01-01},
journal = {INTERNATIONAL JOURNAL OF CANCER},
volume = {132},
number = {2},
pages = {297-307},
abstract = {Serrated adenocarcinoma (SAC) is a recently recognized colorectal cancer
(CRC) subtype accounting for 7.5 to 8.7% of CRCs. It has been shown
that SAC has a poorer prognosis and has different molecular and
immunohistochemical features compared with conventional carcinoma (CC)
but, to date, only one previous study has analyzed its mRNA expression
profile by microarray. Using a different microarray platform, we have
studied the molecular signature of 11 SACs and compared it with that of
15 matched CC with the aim of discerning the functions which
characterize SAC biology and validating, at the mRNA and protein level, the most differentially expressed genes which were also tested using a
validation set of 70 SACs and 70 CCs to assess their diagnostic and
prognostic values. Microarray data showed a higher representation of
morphogenesis-, hypoxia-, cytoskeleton- and vesicle transport-related
functions and also an overexpression of fascin1 (actin-bundling protein
associated with invasion) and the antiapoptotic gene hippocalcin in SAC
all of which were validated both by quantitative real-time PCR (qPCR)
and immunohistochemistry. Fascin1 expression was statistically
associated with KRAS mutation with 88.6% sensitivity and 85.7%
specificity for SAC diagnosis and the positivity of fascin1 or hippocalcin was highly suggestive of SAC diagnosis (sensitivity =
100%). Evaluation of these markers in CRCs showing histological and
molecular characteristics of high-level microsatellite instability
(MSI-H) also helped to distinguish SACs from MSI-H CRCs. Molecular
profiling demonstrates that SAC shows activation of distinct signaling
pathways and that immunohistochemical fascin1 and hippocalcin expression
can be reliably used for its differentiation from other CRC subtypes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Serrated adenocarcinoma (SAC) is a recently recognized colorectal cancer
(CRC) subtype accounting for 7.5 to 8.7% of CRCs. It has been shown
that SAC has a poorer prognosis and has different molecular and
immunohistochemical features compared with conventional carcinoma (CC)
but, to date, only one previous study has analyzed its mRNA expression
profile by microarray. Using a different microarray platform, we have
studied the molecular signature of 11 SACs and compared it with that of
15 matched CC with the aim of discerning the functions which
characterize SAC biology and validating, at the mRNA and protein level, the most differentially expressed genes which were also tested using a
validation set of 70 SACs and 70 CCs to assess their diagnostic and
prognostic values. Microarray data showed a higher representation of
morphogenesis-, hypoxia-, cytoskeleton- and vesicle transport-related
functions and also an overexpression of fascin1 (actin-bundling protein
associated with invasion) and the antiapoptotic gene hippocalcin in SAC
all of which were validated both by quantitative real-time PCR (qPCR)
and immunohistochemistry. Fascin1 expression was statistically
associated with KRAS mutation with 88.6% sensitivity and 85.7%
specificity for SAC diagnosis and the positivity of fascin1 or hippocalcin was highly suggestive of SAC diagnosis (sensitivity =
100%). Evaluation of these markers in CRCs showing histological and
molecular characteristics of high-level microsatellite instability
(MSI-H) also helped to distinguish SACs from MSI-H CRCs. Molecular
profiling demonstrates that SAC shows activation of distinct signaling
pathways and that immunohistochemical fascin1 and hippocalcin expression
can be reliably used for its differentiation from other CRC subtypes.
(CRC) subtype accounting for 7.5 to 8.7% of CRCs. It has been shown
that SAC has a poorer prognosis and has different molecular and
immunohistochemical features compared with conventional carcinoma (CC)
but, to date, only one previous study has analyzed its mRNA expression
profile by microarray. Using a different microarray platform, we have
studied the molecular signature of 11 SACs and compared it with that of
15 matched CC with the aim of discerning the functions which
characterize SAC biology and validating, at the mRNA and protein level, the most differentially expressed genes which were also tested using a
validation set of 70 SACs and 70 CCs to assess their diagnostic and
prognostic values. Microarray data showed a higher representation of
morphogenesis-, hypoxia-, cytoskeleton- and vesicle transport-related
functions and also an overexpression of fascin1 (actin-bundling protein
associated with invasion) and the antiapoptotic gene hippocalcin in SAC
all of which were validated both by quantitative real-time PCR (qPCR)
and immunohistochemistry. Fascin1 expression was statistically
associated with KRAS mutation with 88.6% sensitivity and 85.7%
specificity for SAC diagnosis and the positivity of fascin1 or hippocalcin was highly suggestive of SAC diagnosis (sensitivity =
100%). Evaluation of these markers in CRCs showing histological and
molecular characteristics of high-level microsatellite instability
(MSI-H) also helped to distinguish SACs from MSI-H CRCs. Molecular
profiling demonstrates that SAC shows activation of distinct signaling
pathways and that immunohistochemical fascin1 and hippocalcin expression
can be reliably used for its differentiation from other CRC subtypes.
2012
52.
Yanez, Y.; Grau, E.; Canete, A.; Conesa, A.; Neira, A. Gonzalez; Castel, V.
METHYLATION STATUS IN NEUROBLASTOMA AND ITS PROGNOSTIC VALUE Journal Article
In: PEDIATRIC BLOOD & CANCER, vol. 59, no. 6, SI, pp. 1053-1054, 2012, ISSN: 1545-5009.
@article{ISI:000309754300355,
title = {METHYLATION STATUS IN NEUROBLASTOMA AND ITS PROGNOSTIC VALUE},
author = { Y. Yanez and E. Grau and A. Canete and A. Conesa and A. Gonzalez Neira and V. Castel},
issn = {1545-5009},
year = {2012},
date = {2012-12-01},
journal = {PEDIATRIC BLOOD & CANCER},
volume = {59},
number = {6, SI},
pages = {1053-1054},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
51.
Rizza, S.; Conesa, A.; Juarez, J.; Catara, A.; Navarro, L.; Duran-Vila, N.; Ancillo, G.
In: MOLECULAR PLANT PATHOLOGY, vol. 13, no. 8, pp. 852-864, 2012, ISSN: 1464-6722.
@article{ISI:000308289400005,
title = {Microarray analysis of Etrog citron (Citrus medica L.) reveals changes
in chloroplast, cell wall, peroxidase and symporter activities in
response to viroid infection},
author = { S. Rizza and A. Conesa and J. Juarez and A. Catara and L. Navarro and N. Duran-Vila and G. Ancillo},
url = {http://dx.doi.org/10.1111/j.1364-3703.2012.00794.x},
doi = {10.1111/j.1364-3703.2012.00794.x},
issn = {1464-6722},
year = {2012},
date = {2012-10-01},
journal = {MOLECULAR PLANT PATHOLOGY},
volume = {13},
number = {8},
pages = {852-864},
abstract = {Viroids are small (246401 nucleotides), single-stranded, circular RNA
molecules that infect several crop plants and can cause diseases of
economic importance. Citrus are the hosts in which the largest number of
viroids have been identified. Citrus exocortis viroid (CEVd), the causal
agent of citrus exocortis disease, induces considerable losses in citrus
crops. Changes in the gene expression profile during the early
(pre-symptomatic) and late (post-symptomatic) stages of Etrog citron
infected with CEVd were investigated using a citrus cDNA microarray.
MaSigPro analysis was performed and, on the basis of gene expression
profiles as a function of the time after infection, the differentially
expressed genes were classified into five clusters. FatiScan analysis
revealed significant enrichment of functional categories for each
cluster, indicating that viroid infection triggers important changes in
chloroplast, cell wall, peroxidase and symporter activities.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Viroids are small (246401 nucleotides), single-stranded, circular RNA
molecules that infect several crop plants and can cause diseases of
economic importance. Citrus are the hosts in which the largest number of
viroids have been identified. Citrus exocortis viroid (CEVd), the causal
agent of citrus exocortis disease, induces considerable losses in citrus
crops. Changes in the gene expression profile during the early
(pre-symptomatic) and late (post-symptomatic) stages of Etrog citron
infected with CEVd were investigated using a citrus cDNA microarray.
MaSigPro analysis was performed and, on the basis of gene expression
profiles as a function of the time after infection, the differentially
expressed genes were classified into five clusters. FatiScan analysis
revealed significant enrichment of functional categories for each
cluster, indicating that viroid infection triggers important changes in
chloroplast, cell wall, peroxidase and symporter activities.
molecules that infect several crop plants and can cause diseases of
economic importance. Citrus are the hosts in which the largest number of
viroids have been identified. Citrus exocortis viroid (CEVd), the causal
agent of citrus exocortis disease, induces considerable losses in citrus
crops. Changes in the gene expression profile during the early
(pre-symptomatic) and late (post-symptomatic) stages of Etrog citron
infected with CEVd were investigated using a citrus cDNA microarray.
MaSigPro analysis was performed and, on the basis of gene expression
profiles as a function of the time after infection, the differentially
expressed genes were classified into five clusters. FatiScan analysis
revealed significant enrichment of functional categories for each
cluster, indicating that viroid infection triggers important changes in
chloroplast, cell wall, peroxidase and symporter activities.
50.
Garcia-Alcalde, F.; Okonechnikov, K.; Carbonell, J.; Cruz, L. M.; Goetz, S.; Tarazona, S.; Dopazo, J.; Meyer, T. F.; Conesa, A.
Qualimap: evaluating next-generation sequencing alignment data Journal Article
In: BIOINFORMATICS, vol. 28, no. 20, pp. 2678-2679, 2012, ISSN: 1367-4803.
@article{ISI:000309881200016,
title = {Qualimap: evaluating next-generation sequencing alignment data},
author = { F. Garcia-Alcalde and K. Okonechnikov and J. Carbonell and L. M. Cruz and S. Goetz and S. Tarazona and J. Dopazo and T. F. Meyer and A. Conesa},
url = {http://dx.doi.org/10.1093/bioinformatics/bts503},
doi = {10.1093/bioinformatics/bts503},
issn = {1367-4803},
year = {2012},
date = {2012-10-01},
journal = {BIOINFORMATICS},
volume = {28},
number = {20},
pages = {2678-2679},
abstract = {Motivation: The sequence alignment/map (SAM) and the binary
alignment/map (BAM) formats have become the standard method of
representation of nucleotide sequence alignments for next-generation
sequencing data. SAM/BAM files usually contain information from tens to
hundreds of millions of reads. Often, the sequencing technology, protocol and/or the selected mapping algorithm introduce some unwanted
biases in these data. The systematic detection of such biases is a
non-trivial task that is crucial to drive appropriate downstream
analyses.
Results: We have developed Qualimap, a Java application that supports
user-friendly quality control of mapping data, by considering sequence
features and their genomic properties. Qualimap takes sequence alignment
data and provides graphical and statistical analyses for the evaluation
of data. Such quality-control data are vital for highlighting problems
in the sequencing and/or mapping processes, which must be addressed
prior to further analyses.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Motivation: The sequence alignment/map (SAM) and the binary
alignment/map (BAM) formats have become the standard method of
representation of nucleotide sequence alignments for next-generation
sequencing data. SAM/BAM files usually contain information from tens to
hundreds of millions of reads. Often, the sequencing technology, protocol and/or the selected mapping algorithm introduce some unwanted
biases in these data. The systematic detection of such biases is a
non-trivial task that is crucial to drive appropriate downstream
analyses.
Results: We have developed Qualimap, a Java application that supports
user-friendly quality control of mapping data, by considering sequence
features and their genomic properties. Qualimap takes sequence alignment
data and provides graphical and statistical analyses for the evaluation
of data. Such quality-control data are vital for highlighting problems
in the sequencing and/or mapping processes, which must be addressed
prior to further analyses.
alignment/map (BAM) formats have become the standard method of
representation of nucleotide sequence alignments for next-generation
sequencing data. SAM/BAM files usually contain information from tens to
hundreds of millions of reads. Often, the sequencing technology, protocol and/or the selected mapping algorithm introduce some unwanted
biases in these data. The systematic detection of such biases is a
non-trivial task that is crucial to drive appropriate downstream
analyses.
Results: We have developed Qualimap, a Java application that supports
user-friendly quality control of mapping data, by considering sequence
features and their genomic properties. Qualimap takes sequence alignment
data and provides graphical and statistical analyses for the evaluation
of data. Such quality-control data are vital for highlighting problems
in the sequencing and/or mapping processes, which must be addressed
prior to further analyses.
49.
Fernandez, P.; Soria, M.; Blesa, D.; DiRienzo, J.; Moschen, S.; Rivarola, M.; Clavijo, B. Jose; Gonzalez, S.; Peluffo, L.; Principi, D.; Dosio, G.; Aguirrezabal, L.; Garcia-Garcia, F.; Conesa, A.; Hopp, E.; Dopazo, J.; Heinz, R. Amelia; Paniego, N.
In: PLOS ONE, vol. 7, no. 10, 2012, ISSN: 1932-6203.
@article{ISI:000310262500003,
title = {Development, Characterization and Experimental Validation of a
Cultivated Sunflower (Helianthus annuus L.) Gene Expression
Oligonucleotide Microarray},
author = { P. Fernandez and M. Soria and D. Blesa and J. DiRienzo and S. Moschen and M. Rivarola and B. Jose Clavijo and S. Gonzalez and L. Peluffo and D. Principi and G. Dosio and L. Aguirrezabal and F. Garcia-Garcia and A. Conesa and E. Hopp and J. Dopazo and R. Amelia Heinz and N. Paniego},
url = {http://dx.doi.org/10.1371/journal.pone.0045899},
doi = {10.1371/journal.pone.0045899},
issn = {1932-6203},
year = {2012},
date = {2012-10-01},
journal = {PLOS ONE},
volume = {7},
number = {10},
abstract = {Oligonucleotide-based microarrays with accurate gene coverage represent
a key strategy for transcriptional studies in orphan species such as
sunflower, H. annuus L., which lacks full genome sequences. The goal of
this study was the development and functional annotation of a
comprehensive sunflower unigene collection and the design and validation
of a custom sunflower oligonucleotide-based microarray. A large scale
EST (>130,000 ESTs) curation, assembly and sequence annotation was
performed using Blast2GO (www.blast2go.de). The EST assembly comprises
41,013 putative transcripts (12,924 contigs and 28,089 singletons). The
resulting Sunflower Unigen Resource (SUR version 1.0) was used to design
an oligonucleotide-based Agilent microarray for cultivated sunflower.
This microarray includes a total of 42,326 features: 1,417 Agilent
controls, 74 control probes for sunflower replicated 10 times (740
controls) and 40,169 different non-control probes. Microarray
performance was validated using a model experiment examining the
induction of senescence by water deficit. Pre-processing and
differential expression analysis of Agilent microarrays was performed
using the Bioconductor limma package. The analyses based on p-values
calculated by eBayes (p<0.01) allowed the detection of 558
differentially expressed genes between water stress and control
conditions; from these, ten genes were further validated by qPCR.
Over-represented ontologies were identified using FatiScan in the
Babelomics suite. This work generated a curated and trustable sunflower
unigene collection, and a custom, validated sunflower
oligonucleotide-based microarray using Agilent technology. Both the
curated unigene collection and the validated oligonucleotide microarray
provide key resources for sunflower genome analysis, transcriptional
studies, and molecular breeding for crop improvement.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Oligonucleotide-based microarrays with accurate gene coverage represent
a key strategy for transcriptional studies in orphan species such as
sunflower, H. annuus L., which lacks full genome sequences. The goal of
this study was the development and functional annotation of a
comprehensive sunflower unigene collection and the design and validation
of a custom sunflower oligonucleotide-based microarray. A large scale
EST (>130,000 ESTs) curation, assembly and sequence annotation was
performed using Blast2GO (www.blast2go.de). The EST assembly comprises
41,013 putative transcripts (12,924 contigs and 28,089 singletons). The
resulting Sunflower Unigen Resource (SUR version 1.0) was used to design
an oligonucleotide-based Agilent microarray for cultivated sunflower.
This microarray includes a total of 42,326 features: 1,417 Agilent
controls, 74 control probes for sunflower replicated 10 times (740
controls) and 40,169 different non-control probes. Microarray
performance was validated using a model experiment examining the
induction of senescence by water deficit. Pre-processing and
differential expression analysis of Agilent microarrays was performed
using the Bioconductor limma package. The analyses based on p-values
calculated by eBayes (p<0.01) allowed the detection of 558
differentially expressed genes between water stress and control
conditions; from these, ten genes were further validated by qPCR.
Over-represented ontologies were identified using FatiScan in the
Babelomics suite. This work generated a curated and trustable sunflower
unigene collection, and a custom, validated sunflower
oligonucleotide-based microarray using Agilent technology. Both the
curated unigene collection and the validated oligonucleotide microarray
provide key resources for sunflower genome analysis, transcriptional
studies, and molecular breeding for crop improvement.
a key strategy for transcriptional studies in orphan species such as
sunflower, H. annuus L., which lacks full genome sequences. The goal of
this study was the development and functional annotation of a
comprehensive sunflower unigene collection and the design and validation
of a custom sunflower oligonucleotide-based microarray. A large scale
EST (>130,000 ESTs) curation, assembly and sequence annotation was
performed using Blast2GO (www.blast2go.de). The EST assembly comprises
41,013 putative transcripts (12,924 contigs and 28,089 singletons). The
resulting Sunflower Unigen Resource (SUR version 1.0) was used to design
an oligonucleotide-based Agilent microarray for cultivated sunflower.
This microarray includes a total of 42,326 features: 1,417 Agilent
controls, 74 control probes for sunflower replicated 10 times (740
controls) and 40,169 different non-control probes. Microarray
performance was validated using a model experiment examining the
induction of senescence by water deficit. Pre-processing and
differential expression analysis of Agilent microarrays was performed
using the Bioconductor limma package. The analyses based on p-values
calculated by eBayes (p<0.01) allowed the detection of 558
differentially expressed genes between water stress and control
conditions; from these, ten genes were further validated by qPCR.
Over-represented ontologies were identified using FatiScan in the
Babelomics suite. This work generated a curated and trustable sunflower
unigene collection, and a custom, validated sunflower
oligonucleotide-based microarray using Agilent technology. Both the
curated unigene collection and the validated oligonucleotide microarray
provide key resources for sunflower genome analysis, transcriptional
studies, and molecular breeding for crop improvement.
48.
Agusti, J.; Gimeno, J.; Merelo, P.; Serrano, R.; Cercos, M.; Conesa, A.; Talon, M.; Tadeo, F. R.
In: JOURNAL OF EXPERIMENTAL BOTANY, vol. 63, no. 17, pp. 6079-6091, 2012, ISSN: 0022-0957.
@article{ISI:000310368300003,
title = {Early gene expression events in the laminar abscission zone of
abscission-promoted citrus leaves after a cycle of water
stress/rehydration: involvement of CitbHLH1},
author = { J. Agusti and J. Gimeno and P. Merelo and R. Serrano and M. Cercos and A. Conesa and M. Talon and F. R. Tadeo},
url = {http://dx.doi.org/10.1093/jxb/ers270},
doi = {10.1093/jxb/ers270},
issn = {0022-0957},
year = {2012},
date = {2012-10-01},
journal = {JOURNAL OF EXPERIMENTAL BOTANY},
volume = {63},
number = {17},
pages = {6079-6091},
abstract = {Leaf abscission is a common response of plants to drought stress. Some
species, such as citrus, have evolved a specific behaviour in this
respect, keeping their leaves attached to the plant body during water
stress until this is released by irrigation or rain. This study
successfully reproduced this phenomenon under controlled conditions (24h
of water stress followed by 24h of rehydration) and used it to construct
a suppression subtractive hybridization cDNA library enriched in genes
involved in the early stages of rehydration-promoted leaf abscission
after water stress. Sequencing of the library yielded 314 unigenes, which were spotted onto nylon membranes. Membrane hybridization with
petiole (Pet)- and laminar abscission zone (LAZ)-enriched RNA samples
corresponding to early steps in leaf abscission revealed an almost
exclusive preferential gene expression programme in the LAZ. The data
identified major processes such as protein metabolism, cell-wall
modification, signalling, control of transcription and vesicle
production, and transport as the main biological processes activated in
LAZs during the early steps of rehydration-promoted leaf abscission
after water stress. Based on these findings, a model for the early steps
of citrus leaf abscission is proposed. In addition, it is suggested that
CitbHLH1, the putative citrus orthologue of Arabidopsis BIGPETAL, may
play major roles in the control of abscission-related events in citrus
abscission zones.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Leaf abscission is a common response of plants to drought stress. Some
species, such as citrus, have evolved a specific behaviour in this
respect, keeping their leaves attached to the plant body during water
stress until this is released by irrigation or rain. This study
successfully reproduced this phenomenon under controlled conditions (24h
of water stress followed by 24h of rehydration) and used it to construct
a suppression subtractive hybridization cDNA library enriched in genes
involved in the early stages of rehydration-promoted leaf abscission
after water stress. Sequencing of the library yielded 314 unigenes, which were spotted onto nylon membranes. Membrane hybridization with
petiole (Pet)- and laminar abscission zone (LAZ)-enriched RNA samples
corresponding to early steps in leaf abscission revealed an almost
exclusive preferential gene expression programme in the LAZ. The data
identified major processes such as protein metabolism, cell-wall
modification, signalling, control of transcription and vesicle
production, and transport as the main biological processes activated in
LAZs during the early steps of rehydration-promoted leaf abscission
after water stress. Based on these findings, a model for the early steps
of citrus leaf abscission is proposed. In addition, it is suggested that
CitbHLH1, the putative citrus orthologue of Arabidopsis BIGPETAL, may
play major roles in the control of abscission-related events in citrus
abscission zones.
species, such as citrus, have evolved a specific behaviour in this
respect, keeping their leaves attached to the plant body during water
stress until this is released by irrigation or rain. This study
successfully reproduced this phenomenon under controlled conditions (24h
of water stress followed by 24h of rehydration) and used it to construct
a suppression subtractive hybridization cDNA library enriched in genes
involved in the early stages of rehydration-promoted leaf abscission
after water stress. Sequencing of the library yielded 314 unigenes, which were spotted onto nylon membranes. Membrane hybridization with
petiole (Pet)- and laminar abscission zone (LAZ)-enriched RNA samples
corresponding to early steps in leaf abscission revealed an almost
exclusive preferential gene expression programme in the LAZ. The data
identified major processes such as protein metabolism, cell-wall
modification, signalling, control of transcription and vesicle
production, and transport as the main biological processes activated in
LAZs during the early steps of rehydration-promoted leaf abscission
after water stress. Based on these findings, a model for the early steps
of citrus leaf abscission is proposed. In addition, it is suggested that
CitbHLH1, the putative citrus orthologue of Arabidopsis BIGPETAL, may
play major roles in the control of abscission-related events in citrus
abscission zones.
47.
Nueda, M. J.; Ferrer, A.; Conesa, A.
ARSyN: a method for the identification and removal of systematic noise in multifactorial time course microarray experiments Journal Article
In: BIOSTATISTICS, vol. 13, no. 3, pp. 553-566, 2012, ISSN: 1465-4644.
@article{ISI:000305420000014,
title = {ARSyN: a method for the identification and removal of systematic noise
in multifactorial time course microarray experiments},
author = { M. J. Nueda and A. Ferrer and A. Conesa},
url = {http://dx.doi.org/10.1093/biostatistics/kxr042},
doi = {10.1093/biostatistics/kxr042},
issn = {1465-4644},
year = {2012},
date = {2012-07-01},
journal = {BIOSTATISTICS},
volume = {13},
number = {3},
pages = {553-566},
abstract = {Transcriptomic profiling experiments that aim to the identification of
responsive genes in specific biological conditions are commonly set up
under defined experimental designs that try to assess the effects of
factors and their interactions on gene expression. Data from these
controlled experiments, however, may also contain sources of unwanted
noise that can distort the signal under study, affect the residuals of
applied statistical models, and hamper data analysis. Commonly, normalization methods are applied to transcriptomics data to remove
technical artifacts, but these are normally based on general assumptions
of transcript distribution and greatly ignore both the characteristics
of the experiment under consideration and the coordinative nature of
gene expression. In this paper, we propose a novel methodology, ARSyN, for the preprocessing of microarray data that takes into account these 2
last aspects. By combining analysis of variance (ANOVA) modeling of gene
expression values and multivariate analysis of estimated effects, the
method identifies the nonstructured part of the signal associated to the
experimental factors (the noise within the signal) and the structured
variation of the ANOVA errors (the signal of the noise). By removing
these noise fractions from the original data, we create a filtered data
set that is rich in the information of interest and includes only the
random noise required for inferential analysis. In this work, we focus
on multifactorial time course microarray (MTCM) experiments with 2
factors: one quantitative such as time or dosage and the other
qualitative, as tissue, strain, or treatment. However, the method can be
used in other situations such as experiments with only one factor or
more complex designs with more than 2 factors. The filtered data
obtained after applying ARSyN can be further analyzed with the
appropriate statistical technique to obtain the biological information
required. To evaluate the performance of the filtering strategy, we have
applied different statistical approaches for MTCM analysis to several
real and simulated data sets, studying also the efficiency of these
techniques. By comparing the results obtained with the original and
ARSyN filtered data and also with other filtering techniques, we can
conclude that the proposed method increases the statistical power to
detect biological signals, especially in cases where there are high
levels of structural noise. Software for ARSyN is freely available at
http://www.ua.es/personal/mj.nueda.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Transcriptomic profiling experiments that aim to the identification of
responsive genes in specific biological conditions are commonly set up
under defined experimental designs that try to assess the effects of
factors and their interactions on gene expression. Data from these
controlled experiments, however, may also contain sources of unwanted
noise that can distort the signal under study, affect the residuals of
applied statistical models, and hamper data analysis. Commonly, normalization methods are applied to transcriptomics data to remove
technical artifacts, but these are normally based on general assumptions
of transcript distribution and greatly ignore both the characteristics
of the experiment under consideration and the coordinative nature of
gene expression. In this paper, we propose a novel methodology, ARSyN, for the preprocessing of microarray data that takes into account these 2
last aspects. By combining analysis of variance (ANOVA) modeling of gene
expression values and multivariate analysis of estimated effects, the
method identifies the nonstructured part of the signal associated to the
experimental factors (the noise within the signal) and the structured
variation of the ANOVA errors (the signal of the noise). By removing
these noise fractions from the original data, we create a filtered data
set that is rich in the information of interest and includes only the
random noise required for inferential analysis. In this work, we focus
on multifactorial time course microarray (MTCM) experiments with 2
factors: one quantitative such as time or dosage and the other
qualitative, as tissue, strain, or treatment. However, the method can be
used in other situations such as experiments with only one factor or
more complex designs with more than 2 factors. The filtered data
obtained after applying ARSyN can be further analyzed with the
appropriate statistical technique to obtain the biological information
required. To evaluate the performance of the filtering strategy, we have
applied different statistical approaches for MTCM analysis to several
real and simulated data sets, studying also the efficiency of these
techniques. By comparing the results obtained with the original and
ARSyN filtered data and also with other filtering techniques, we can
conclude that the proposed method increases the statistical power to
detect biological signals, especially in cases where there are high
levels of structural noise. Software for ARSyN is freely available at
http://www.ua.es/personal/mj.nueda.
responsive genes in specific biological conditions are commonly set up
under defined experimental designs that try to assess the effects of
factors and their interactions on gene expression. Data from these
controlled experiments, however, may also contain sources of unwanted
noise that can distort the signal under study, affect the residuals of
applied statistical models, and hamper data analysis. Commonly, normalization methods are applied to transcriptomics data to remove
technical artifacts, but these are normally based on general assumptions
of transcript distribution and greatly ignore both the characteristics
of the experiment under consideration and the coordinative nature of
gene expression. In this paper, we propose a novel methodology, ARSyN, for the preprocessing of microarray data that takes into account these 2
last aspects. By combining analysis of variance (ANOVA) modeling of gene
expression values and multivariate analysis of estimated effects, the
method identifies the nonstructured part of the signal associated to the
experimental factors (the noise within the signal) and the structured
variation of the ANOVA errors (the signal of the noise). By removing
these noise fractions from the original data, we create a filtered data
set that is rich in the information of interest and includes only the
random noise required for inferential analysis. In this work, we focus
on multifactorial time course microarray (MTCM) experiments with 2
factors: one quantitative such as time or dosage and the other
qualitative, as tissue, strain, or treatment. However, the method can be
used in other situations such as experiments with only one factor or
more complex designs with more than 2 factors. The filtered data
obtained after applying ARSyN can be further analyzed with the
appropriate statistical technique to obtain the biological information
required. To evaluate the performance of the filtering strategy, we have
applied different statistical approaches for MTCM analysis to several
real and simulated data sets, studying also the efficiency of these
techniques. By comparing the results obtained with the original and
ARSyN filtered data and also with other filtering techniques, we can
conclude that the proposed method increases the statistical power to
detect biological signals, especially in cases where there are high
levels of structural noise. Software for ARSyN is freely available at
http://www.ua.es/personal/mj.nueda.
46.
Lin, C. J.; Irmer, H.; Tarazona, S.; Olbermann, P.; Krappmann, S.; Conesa, A.; Braus, G.
Regulatory proteins in the opportunistic human pathogen Aspergillus fumigatus Journal Article
In: MYCOSES, vol. 55, no. 4, SI, pp. 135-136, 2012, ISSN: 0933-7407.
@article{ISI:000305069800421,
title = {Regulatory proteins in the opportunistic human pathogen Aspergillus
fumigatus},
author = { C. J. Lin and H. Irmer and S. Tarazona and P. Olbermann and S. Krappmann and A. Conesa and G. Braus},
issn = {0933-7407},
year = {2012},
date = {2012-06-01},
journal = {MYCOSES},
volume = {55},
number = {4, SI},
pages = {135-136},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
45.
Jaime, M. D. L. A.; Lopez-Llorca, L. Vicente; Conesa, A.; Lee, A. Y.; Proctor, M.; Heisler, L. E.; Gebbia, M.; Giaever, G.; Westwood, J. T.; Nislow, C.
Identification of yeast genes that confer resistance to chitosan oligosaccharide (COS) using chemogenomics Journal Article
In: BMC GENOMICS, vol. 13, 2012, ISSN: 1471-2164.
@article{ISI:000311518100001,
title = {Identification of yeast genes that confer resistance to chitosan
oligosaccharide (COS) using chemogenomics},
author = { M. D. L. A. Jaime and L. Vicente Lopez-Llorca and A. Conesa and A. Y. Lee and M. Proctor and L. E. Heisler and M. Gebbia and G. Giaever and J. T. Westwood and C. Nislow},
url = {http://dx.doi.org/10.1186/1471-2164-13-267},
doi = {10.1186/1471-2164-13-267},
issn = {1471-2164},
year = {2012},
date = {2012-06-01},
journal = {BMC GENOMICS},
volume = {13},
abstract = {Background: Chitosan oligosaccharide (COS), a deacetylated derivative of
chitin, is an abundant, and renewable natural polymer. COS has higher
antimicrobial properties than chitosan and is presumed to act by
disrupting/permeabilizing the cell membranes of bacteria, yeast and
fungi. COS is relatively non-toxic to mammals. By identifying the
molecular and genetic targets of COS, we hope to gain a better
understanding of the antifungal mode of action of COS.
Results: Three different chemogenomic fitness assays, haploinsufficiency
(HIP), homozygous deletion (HOP), and multicopy suppression (MSP)
profiling were combined with a transcriptomic analysis to gain insight
in to the mode of action and mechanisms of resistance to chitosan
oligosaccharides. The fitness assays identified 39 yeast deletion
strains sensitive to COS and 21 suppressors of COS sensitivity. The
genes identified are involved in processes such as RNA biology
(transcription, translation and regulatory mechanisms), membrane
functions (e.g. signalling, transport and targeting), membrane
structural components, cell division, and proteasome processes. The
transcriptomes of control wild type and 5 suppressor strains
overexpressing ARL1, BCK2, ERG24, MSG5, or RBA50, were analyzed in the
presence and absence of COS. Some of the up-regulated transcripts in the
suppressor overexpressing strains exposed to COS included genes involved
in transcription, cell cycle, stress response and the Ras signal
transduction pathway. Down-regulated transcripts included those encoding
protein folding components and respiratory chain proteins. The
COS-induced transcriptional response is distinct from previously
described environmental stress responses (i.e. thermal, salt, osmotic
and oxidative stress) and pre-treatment with these well characterized
environmental stressors provided little or any resistance to COS.
Conclusions: Overexpression of the ARL1 gene, a member of the Ras
superfamily that regulates membrane trafficking, provides protection
against COS-induced cell membrane permeability and damage. We found that
the ARL1 COS-resistant over-expression strain was as sensitive to
Amphotericin B, Fluconazole and Terbinafine as the wild type cells and
that when COS and Fluconazole are used in combination they act in a
synergistic fashion. The gene targets of COS identified in this study
indicate that COS's mechanism of action is different from other commonly
studied fungicides that target membranes, suggesting that COS may be an
effective fungicide for drug-resistant fungal pathogens.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Chitosan oligosaccharide (COS), a deacetylated derivative of
chitin, is an abundant, and renewable natural polymer. COS has higher
antimicrobial properties than chitosan and is presumed to act by
disrupting/permeabilizing the cell membranes of bacteria, yeast and
fungi. COS is relatively non-toxic to mammals. By identifying the
molecular and genetic targets of COS, we hope to gain a better
understanding of the antifungal mode of action of COS.
Results: Three different chemogenomic fitness assays, haploinsufficiency
(HIP), homozygous deletion (HOP), and multicopy suppression (MSP)
profiling were combined with a transcriptomic analysis to gain insight
in to the mode of action and mechanisms of resistance to chitosan
oligosaccharides. The fitness assays identified 39 yeast deletion
strains sensitive to COS and 21 suppressors of COS sensitivity. The
genes identified are involved in processes such as RNA biology
(transcription, translation and regulatory mechanisms), membrane
functions (e.g. signalling, transport and targeting), membrane
structural components, cell division, and proteasome processes. The
transcriptomes of control wild type and 5 suppressor strains
overexpressing ARL1, BCK2, ERG24, MSG5, or RBA50, were analyzed in the
presence and absence of COS. Some of the up-regulated transcripts in the
suppressor overexpressing strains exposed to COS included genes involved
in transcription, cell cycle, stress response and the Ras signal
transduction pathway. Down-regulated transcripts included those encoding
protein folding components and respiratory chain proteins. The
COS-induced transcriptional response is distinct from previously
described environmental stress responses (i.e. thermal, salt, osmotic
and oxidative stress) and pre-treatment with these well characterized
environmental stressors provided little or any resistance to COS.
Conclusions: Overexpression of the ARL1 gene, a member of the Ras
superfamily that regulates membrane trafficking, provides protection
against COS-induced cell membrane permeability and damage. We found that
the ARL1 COS-resistant over-expression strain was as sensitive to
Amphotericin B, Fluconazole and Terbinafine as the wild type cells and
that when COS and Fluconazole are used in combination they act in a
synergistic fashion. The gene targets of COS identified in this study
indicate that COS's mechanism of action is different from other commonly
studied fungicides that target membranes, suggesting that COS may be an
effective fungicide for drug-resistant fungal pathogens.
chitin, is an abundant, and renewable natural polymer. COS has higher
antimicrobial properties than chitosan and is presumed to act by
disrupting/permeabilizing the cell membranes of bacteria, yeast and
fungi. COS is relatively non-toxic to mammals. By identifying the
molecular and genetic targets of COS, we hope to gain a better
understanding of the antifungal mode of action of COS.
Results: Three different chemogenomic fitness assays, haploinsufficiency
(HIP), homozygous deletion (HOP), and multicopy suppression (MSP)
profiling were combined with a transcriptomic analysis to gain insight
in to the mode of action and mechanisms of resistance to chitosan
oligosaccharides. The fitness assays identified 39 yeast deletion
strains sensitive to COS and 21 suppressors of COS sensitivity. The
genes identified are involved in processes such as RNA biology
(transcription, translation and regulatory mechanisms), membrane
functions (e.g. signalling, transport and targeting), membrane
structural components, cell division, and proteasome processes. The
transcriptomes of control wild type and 5 suppressor strains
overexpressing ARL1, BCK2, ERG24, MSG5, or RBA50, were analyzed in the
presence and absence of COS. Some of the up-regulated transcripts in the
suppressor overexpressing strains exposed to COS included genes involved
in transcription, cell cycle, stress response and the Ras signal
transduction pathway. Down-regulated transcripts included those encoding
protein folding components and respiratory chain proteins. The
COS-induced transcriptional response is distinct from previously
described environmental stress responses (i.e. thermal, salt, osmotic
and oxidative stress) and pre-treatment with these well characterized
environmental stressors provided little or any resistance to COS.
Conclusions: Overexpression of the ARL1 gene, a member of the Ras
superfamily that regulates membrane trafficking, provides protection
against COS-induced cell membrane permeability and damage. We found that
the ARL1 COS-resistant over-expression strain was as sensitive to
Amphotericin B, Fluconazole and Terbinafine as the wild type cells and
that when COS and Fluconazole are used in combination they act in a
synergistic fashion. The gene targets of COS identified in this study
indicate that COS's mechanism of action is different from other commonly
studied fungicides that target membranes, suggesting that COS may be an
effective fungicide for drug-resistant fungal pathogens.
44.
Perez-Quintero, A. L.; Sablok, G.; Tatarinova, T. V.; Conesa, A.; Kuo, J.; Lopez, C.
Mining of miRNAs and potential targets from gene oriented clusters of transcripts sequences of the anti-malarial plant, Artemisia annua Journal Article
In: BIOTECHNOLOGY LETTERS, vol. 34, no. 4, pp. 737-745, 2012, ISSN: 0141-5492.
@article{ISI:000301295900020,
title = {Mining of miRNAs and potential targets from gene oriented clusters of
transcripts sequences of the anti-malarial plant, Artemisia annua},
author = { A. L. Perez-Quintero and G. Sablok and T. V. Tatarinova and A. Conesa and J. Kuo and C. Lopez},
url = {http://dx.doi.org/10.1007/s10529-011-0808-0},
doi = {10.1007/s10529-011-0808-0},
issn = {0141-5492},
year = {2012},
date = {2012-04-01},
journal = {BIOTECHNOLOGY LETTERS},
volume = {34},
number = {4},
pages = {737-745},
abstract = {miRNAs involved in the biosynthesis of artemisinin, an anti-malarial
compound form the plant Artemisia annua, have been identified using
computational approaches to find conserved pre-miRNAs in available A.
annua UniGene collections. Eleven pre-miRNAs were found from nine
families. Targets predicted for these miRNAs were mainly transcription
factors for conserved miRNAs. No target genes involved in artemisinin
biosynthesis were found. However, miR390 was predicted to target a gene
involved in the trichome development, which is the site of synthesis of
artemisinin and could be a candidate for genetic transformation aiming
to increase the content of artemisinin. Phylogenetic analyses were
carried out to determinate the relation between A. annua and other plant
pre-miRNAs: the pre-miRNA-based phylogenetic trees failed to correspond
to known phylogenies, suggesting that pre-miRNA primary sequences may be
too variable to accurately predict phylogenetic relations.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
miRNAs involved in the biosynthesis of artemisinin, an anti-malarial
compound form the plant Artemisia annua, have been identified using
computational approaches to find conserved pre-miRNAs in available A.
annua UniGene collections. Eleven pre-miRNAs were found from nine
families. Targets predicted for these miRNAs were mainly transcription
factors for conserved miRNAs. No target genes involved in artemisinin
biosynthesis were found. However, miR390 was predicted to target a gene
involved in the trichome development, which is the site of synthesis of
artemisinin and could be a candidate for genetic transformation aiming
to increase the content of artemisinin. Phylogenetic analyses were
carried out to determinate the relation between A. annua and other plant
pre-miRNAs: the pre-miRNA-based phylogenetic trees failed to correspond
to known phylogenies, suggesting that pre-miRNA primary sequences may be
too variable to accurately predict phylogenetic relations.
compound form the plant Artemisia annua, have been identified using
computational approaches to find conserved pre-miRNAs in available A.
annua UniGene collections. Eleven pre-miRNAs were found from nine
families. Targets predicted for these miRNAs were mainly transcription
factors for conserved miRNAs. No target genes involved in artemisinin
biosynthesis were found. However, miR390 was predicted to target a gene
involved in the trichome development, which is the site of synthesis of
artemisinin and could be a candidate for genetic transformation aiming
to increase the content of artemisinin. Phylogenetic analyses were
carried out to determinate the relation between A. annua and other plant
pre-miRNAs: the pre-miRNA-based phylogenetic trees failed to correspond
to known phylogenies, suggesting that pre-miRNA primary sequences may be
too variable to accurately predict phylogenetic relations.
43.
Oppert, B.; Dowd, S. E.; Bouffard, P.; Li, L.; Conesa, A.; Lorenzen, M. D.; Toutges, M.; Marshall, J.; Huestis, D. L.; Fabrick, J.; Oppert, C.; Jurat-Fuentes, J. L.
Transcriptome Profiling of the Intoxication Response of Tenebrio molitor Larvae to Bacillus thuringiensis Cry3Aa Protoxin Journal Article
In: PLOS ONE, vol. 7, no. 4, 2012, ISSN: 1932-6203.
@article{ISI:000305345200011,
title = {Transcriptome Profiling of the Intoxication Response of Tenebrio molitor
Larvae to Bacillus thuringiensis Cry3Aa Protoxin},
author = { B. Oppert and S. E. Dowd and P. Bouffard and L. Li and A. Conesa and M. D. Lorenzen and M. Toutges and J. Marshall and D. L. Huestis and J. Fabrick and C. Oppert and J. L. Jurat-Fuentes},
url = {http://dx.doi.org/10.1371/journal.pone.0034624},
doi = {10.1371/journal.pone.0034624},
issn = {1932-6203},
year = {2012},
date = {2012-04-01},
journal = {PLOS ONE},
volume = {7},
number = {4},
abstract = {Bacillus thuringiensis (Bt) crystal (Cry) proteins are effective against
a select number of insect pests, but improvements are needed to increase
efficacy and decrease time to mortality for coleopteran pests. To gain
insight into the Bt intoxication process in Coleoptera, we performed
RNA-Seq on cDNA generated from the guts of Tenebrio molitor larvae that
consumed either a control diet or a diet containing Cry3Aa protoxin.
Approximately 134,090 and 124,287 sequence reads from the control and
Cry3Aa-treated groups were assembled into 1,318 and 1,140 contigs, respectively. Enrichment analyses indicated that functions associated
with mitochondrial respiration, signalling, maintenance of cell
structure, membrane integrity, protein recycling/synthesis, and glycosyl
hydrolases were significantly increased in Cry3Aa-treated larvae, whereas functions associated with many metabolic processes were reduced, especially glycolysis, tricarboxylic acid cycle, and fatty acid
synthesis. Microarray analysis was used to evaluate temporal changes in
gene expression after 6, 12 or 24 h of Cry3Aa exposure. Overall, microarray analysis indicated that transcripts related to allergens, chitin-binding proteins, glycosyl hydrolases, and tubulins were induced, and those related to immunity and metabolism were repressed in
Cry3Aa-intoxicated larvae. The 24 h microarray data validated most of
the RNA-Seq data. Of the three intoxication intervals, larvae
demonstrated more differential expression of transcripts after 12 h
exposure to Cry3Aa. Gene expression examined by three different methods
in control vs. Cry3Aa-treated larvae at the 24 h time point indicated
that transcripts encoding proteins with chitin-binding domain 3 were the
most differentially expressed in Cry3Aa-intoxicated larvae. Overall, the
data suggest that T. molitor larvae mount a complex response to Cry3Aa
during the initial 24 h of intoxication. Data from this study represent
the largest genetic sequence dataset for T. molitor to date.
Furthermore, the methods in this study are useful for comparative
analyses in organisms lacking a sequenced genome.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bacillus thuringiensis (Bt) crystal (Cry) proteins are effective against
a select number of insect pests, but improvements are needed to increase
efficacy and decrease time to mortality for coleopteran pests. To gain
insight into the Bt intoxication process in Coleoptera, we performed
RNA-Seq on cDNA generated from the guts of Tenebrio molitor larvae that
consumed either a control diet or a diet containing Cry3Aa protoxin.
Approximately 134,090 and 124,287 sequence reads from the control and
Cry3Aa-treated groups were assembled into 1,318 and 1,140 contigs, respectively. Enrichment analyses indicated that functions associated
with mitochondrial respiration, signalling, maintenance of cell
structure, membrane integrity, protein recycling/synthesis, and glycosyl
hydrolases were significantly increased in Cry3Aa-treated larvae, whereas functions associated with many metabolic processes were reduced, especially glycolysis, tricarboxylic acid cycle, and fatty acid
synthesis. Microarray analysis was used to evaluate temporal changes in
gene expression after 6, 12 or 24 h of Cry3Aa exposure. Overall, microarray analysis indicated that transcripts related to allergens, chitin-binding proteins, glycosyl hydrolases, and tubulins were induced, and those related to immunity and metabolism were repressed in
Cry3Aa-intoxicated larvae. The 24 h microarray data validated most of
the RNA-Seq data. Of the three intoxication intervals, larvae
demonstrated more differential expression of transcripts after 12 h
exposure to Cry3Aa. Gene expression examined by three different methods
in control vs. Cry3Aa-treated larvae at the 24 h time point indicated
that transcripts encoding proteins with chitin-binding domain 3 were the
most differentially expressed in Cry3Aa-intoxicated larvae. Overall, the
data suggest that T. molitor larvae mount a complex response to Cry3Aa
during the initial 24 h of intoxication. Data from this study represent
the largest genetic sequence dataset for T. molitor to date.
Furthermore, the methods in this study are useful for comparative
analyses in organisms lacking a sequenced genome.
a select number of insect pests, but improvements are needed to increase
efficacy and decrease time to mortality for coleopteran pests. To gain
insight into the Bt intoxication process in Coleoptera, we performed
RNA-Seq on cDNA generated from the guts of Tenebrio molitor larvae that
consumed either a control diet or a diet containing Cry3Aa protoxin.
Approximately 134,090 and 124,287 sequence reads from the control and
Cry3Aa-treated groups were assembled into 1,318 and 1,140 contigs, respectively. Enrichment analyses indicated that functions associated
with mitochondrial respiration, signalling, maintenance of cell
structure, membrane integrity, protein recycling/synthesis, and glycosyl
hydrolases were significantly increased in Cry3Aa-treated larvae, whereas functions associated with many metabolic processes were reduced, especially glycolysis, tricarboxylic acid cycle, and fatty acid
synthesis. Microarray analysis was used to evaluate temporal changes in
gene expression after 6, 12 or 24 h of Cry3Aa exposure. Overall, microarray analysis indicated that transcripts related to allergens, chitin-binding proteins, glycosyl hydrolases, and tubulins were induced, and those related to immunity and metabolism were repressed in
Cry3Aa-intoxicated larvae. The 24 h microarray data validated most of
the RNA-Seq data. Of the three intoxication intervals, larvae
demonstrated more differential expression of transcripts after 12 h
exposure to Cry3Aa. Gene expression examined by three different methods
in control vs. Cry3Aa-treated larvae at the 24 h time point indicated
that transcripts encoding proteins with chitin-binding domain 3 were the
most differentially expressed in Cry3Aa-intoxicated larvae. Overall, the
data suggest that T. molitor larvae mount a complex response to Cry3Aa
during the initial 24 h of intoxication. Data from this study represent
the largest genetic sequence dataset for T. molitor to date.
Furthermore, the methods in this study are useful for comparative
analyses in organisms lacking a sequenced genome.
42.
Carcel-Trullols, J.; Aguilar-Gallardo, C.; Garcia-Alcalde, F.; Pardo-Cea, M. Angel; Dopazo, J.; Conesa, A.; Simon, C.
Transdifferentiation of MALME-3M and MCF-7 Cells toward Adipocyte-like Cells is Dependent on Clathrin-mediated Endocytosis Journal Article
In: SPRINGERPLUS, vol. 1, 2012, ISSN: 2193-1801.
@article{ISI:000209459000044,
title = {Transdifferentiation of MALME-3M and MCF-7 Cells toward Adipocyte-like
Cells is Dependent on Clathrin-mediated Endocytosis},
author = { J. Carcel-Trullols and C. Aguilar-Gallardo and F. Garcia-Alcalde and M. Angel Pardo-Cea and J. Dopazo and A. Conesa and C. Simon},
url = {http://dx.doi.org/10.1186/2193-1801-1-44},
doi = {10.1186/2193-1801-1-44},
issn = {2193-1801},
year = {2012},
date = {2012-01-01},
journal = {SPRINGERPLUS},
volume = {1},
abstract = {Enforced cell transdifferentiation of human cancer cells is a promising
alternative to conventional chemotherapy. We previously identified
albumin-associated lipid-and, more specifically, saturated fatty
acid-induced transdifferentiation programs in human cancer cells
(HCCLs). In this study, we further characterized the adipocyte-like
cells, resulting from the transdifferentiation of human cancer cell
lines MCF-7 and MALME-3M, and proposed a common mechanistic approach for
these transdifferentiating programs. We showed the loss of pigmentation
in MALME-3M cells treated with albumin-associated lipids, based on
electron microscopic analysis, and the overexpression of perilipin 2
(PLIN2) by western blotting in MALME-3M and MCF-7 cells treated with
unsaturated fatty acids. Comparing the gene expression profiles of naive
melanoma MALME-3M cells and albumin-associated lipid-treated cells, based on RNA sequencing, we confirmed the transcriptional upregulation
of some key adipogenic gene markers and also an alternative splicing of
the adipogenic master regulator PPARG, that is probably related to the
reported up regulated expression of the protein. Most importantly, these
results also showed the upregulation of genes responsible for Clathrin
(CLTC) and other adaptor-related proteins. An increase in CLTC
expression in the transdifferentiated cells was confirmed by western
blotting. Inactivation of CLTC by chlorpromazine (CHP), an inhibitor of
CTLC mediated endocytosis (CME), and gene silencing by siRNAs, partially
reversed the accumulation of neutral lipids observed in the
transdifferentiated cells. These findings give a deeper insight into the
phenotypic changes observed in HCCL to adipocyte-like
transdifferentiation and point towards CME as a key pathway in distinct
transdifferentiation programs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Enforced cell transdifferentiation of human cancer cells is a promising
alternative to conventional chemotherapy. We previously identified
albumin-associated lipid-and, more specifically, saturated fatty
acid-induced transdifferentiation programs in human cancer cells
(HCCLs). In this study, we further characterized the adipocyte-like
cells, resulting from the transdifferentiation of human cancer cell
lines MCF-7 and MALME-3M, and proposed a common mechanistic approach for
these transdifferentiating programs. We showed the loss of pigmentation
in MALME-3M cells treated with albumin-associated lipids, based on
electron microscopic analysis, and the overexpression of perilipin 2
(PLIN2) by western blotting in MALME-3M and MCF-7 cells treated with
unsaturated fatty acids. Comparing the gene expression profiles of naive
melanoma MALME-3M cells and albumin-associated lipid-treated cells, based on RNA sequencing, we confirmed the transcriptional upregulation
of some key adipogenic gene markers and also an alternative splicing of
the adipogenic master regulator PPARG, that is probably related to the
reported up regulated expression of the protein. Most importantly, these
results also showed the upregulation of genes responsible for Clathrin
(CLTC) and other adaptor-related proteins. An increase in CLTC
expression in the transdifferentiated cells was confirmed by western
blotting. Inactivation of CLTC by chlorpromazine (CHP), an inhibitor of
CTLC mediated endocytosis (CME), and gene silencing by siRNAs, partially
reversed the accumulation of neutral lipids observed in the
transdifferentiated cells. These findings give a deeper insight into the
phenotypic changes observed in HCCL to adipocyte-like
transdifferentiation and point towards CME as a key pathway in distinct
transdifferentiation programs.
alternative to conventional chemotherapy. We previously identified
albumin-associated lipid-and, more specifically, saturated fatty
acid-induced transdifferentiation programs in human cancer cells
(HCCLs). In this study, we further characterized the adipocyte-like
cells, resulting from the transdifferentiation of human cancer cell
lines MCF-7 and MALME-3M, and proposed a common mechanistic approach for
these transdifferentiating programs. We showed the loss of pigmentation
in MALME-3M cells treated with albumin-associated lipids, based on
electron microscopic analysis, and the overexpression of perilipin 2
(PLIN2) by western blotting in MALME-3M and MCF-7 cells treated with
unsaturated fatty acids. Comparing the gene expression profiles of naive
melanoma MALME-3M cells and albumin-associated lipid-treated cells, based on RNA sequencing, we confirmed the transcriptional upregulation
of some key adipogenic gene markers and also an alternative splicing of
the adipogenic master regulator PPARG, that is probably related to the
reported up regulated expression of the protein. Most importantly, these
results also showed the upregulation of genes responsible for Clathrin
(CLTC) and other adaptor-related proteins. An increase in CLTC
expression in the transdifferentiated cells was confirmed by western
blotting. Inactivation of CLTC by chlorpromazine (CHP), an inhibitor of
CTLC mediated endocytosis (CME), and gene silencing by siRNAs, partially
reversed the accumulation of neutral lipids observed in the
transdifferentiated cells. These findings give a deeper insight into the
phenotypic changes observed in HCCL to adipocyte-like
transdifferentiation and point towards CME as a key pathway in distinct
transdifferentiation programs.
41.
Leida, C.; Conesa, A.; Llacer, G.; Badenes, M. Luisa; Rios, G.
Histone modifications and expression of DAM6 gene in peach are modulated during bud dormancy release in a cultivar-dependent manner Journal Article
In: NEW PHYTOLOGIST, vol. 193, no. 1, pp. 67-80, 2012, ISSN: 0028-646X.
@article{ISI:000298300800012,
title = {Histone modifications and expression of DAM6 gene in peach are modulated
during bud dormancy release in a cultivar-dependent manner},
author = { C. Leida and A. Conesa and G. Llacer and M. Luisa Badenes and G. Rios},
url = {http://dx.doi.org/10.1111/j.1469-8137.2011.03863.x},
doi = {10.1111/j.1469-8137.2011.03863.x},
issn = {0028-646X},
year = {2012},
date = {2012-01-01},
journal = {NEW PHYTOLOGIST},
volume = {193},
number = {1},
pages = {67-80},
abstract = {Bud dormancy release in many woody perennial plants responds to the
seasonal accumulation of chilling stimulus. MADS-box transcription
factors encoded by DORMANCY ASSOCIATED MADS-box (DAM) genes in peach
(Prunus persica) are implicated in this pathway, but other regulatory
factors remain to be identified. In addition, the regulation of DAM gene
expression is not well known at the molecular level. A microarray
hybridization approach was performed to identify genes whose expression
correlates with the bud dormancy-related behaviour in 10 different peach
cultivars. Histone modifications in DAM6 gene were investigated by
chromatin immunoprecipitation in two different cultivars. The expression
of DAM4DAM6 and several genes related to abscisic acid and drought
stress response correlated with the dormancy behaviour of peach
cultivars. The trimethylation of histone H3 at K27 in the DAM6 promoter, coding region and the second large intron was preceded by a decrease in
acetylated H3 and trimethylated H3K4 in the region of translation start, coinciding with repression of DAM6 during dormancy release. Analysis of
chromatin modifications reinforced the role of epigenetic mechanisms in
DAM6 regulation and bud dormancy release, and highlighted common
features with the vernalization process in Arabidopsis thaliana and
cereals.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bud dormancy release in many woody perennial plants responds to the
seasonal accumulation of chilling stimulus. MADS-box transcription
factors encoded by DORMANCY ASSOCIATED MADS-box (DAM) genes in peach
(Prunus persica) are implicated in this pathway, but other regulatory
factors remain to be identified. In addition, the regulation of DAM gene
expression is not well known at the molecular level. A microarray
hybridization approach was performed to identify genes whose expression
correlates with the bud dormancy-related behaviour in 10 different peach
cultivars. Histone modifications in DAM6 gene were investigated by
chromatin immunoprecipitation in two different cultivars. The expression
of DAM4DAM6 and several genes related to abscisic acid and drought
stress response correlated with the dormancy behaviour of peach
cultivars. The trimethylation of histone H3 at K27 in the DAM6 promoter, coding region and the second large intron was preceded by a decrease in
acetylated H3 and trimethylated H3K4 in the region of translation start, coinciding with repression of DAM6 during dormancy release. Analysis of
chromatin modifications reinforced the role of epigenetic mechanisms in
DAM6 regulation and bud dormancy release, and highlighted common
features with the vernalization process in Arabidopsis thaliana and
cereals.
seasonal accumulation of chilling stimulus. MADS-box transcription
factors encoded by DORMANCY ASSOCIATED MADS-box (DAM) genes in peach
(Prunus persica) are implicated in this pathway, but other regulatory
factors remain to be identified. In addition, the regulation of DAM gene
expression is not well known at the molecular level. A microarray
hybridization approach was performed to identify genes whose expression
correlates with the bud dormancy-related behaviour in 10 different peach
cultivars. Histone modifications in DAM6 gene were investigated by
chromatin immunoprecipitation in two different cultivars. The expression
of DAM4DAM6 and several genes related to abscisic acid and drought
stress response correlated with the dormancy behaviour of peach
cultivars. The trimethylation of histone H3 at K27 in the DAM6 promoter, coding region and the second large intron was preceded by a decrease in
acetylated H3 and trimethylated H3K4 in the region of translation start, coinciding with repression of DAM6 during dormancy release. Analysis of
chromatin modifications reinforced the role of epigenetic mechanisms in
DAM6 regulation and bud dormancy release, and highlighted common
features with the vernalization process in Arabidopsis thaliana and
cereals.
40.
Tarazona, S.; Prado-Lopez, S.; Dopazo, J.; Ferrer, A.; Conesa, A.
Variable selection for multifactorial genomic data Journal Article
In: CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS, vol. 110, no. 1, pp. 113-122, 2012, ISSN: 0169-7439.
@article{ISI:000299712500014,
title = {Variable selection for multifactorial genomic data},
author = { S. Tarazona and S. Prado-Lopez and J. Dopazo and A. Ferrer and A. Conesa},
url = {http://dx.doi.org/10.1016/j.chemolab.2011.10.012},
doi = {10.1016/j.chemolab.2011.10.012},
issn = {0169-7439},
year = {2012},
date = {2012-01-01},
journal = {CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS},
volume = {110},
number = {1},
pages = {113-122},
abstract = {Dimension reduction techniques are used to explore genomic data. Due to
the large number of variables (genes) included in this kind of studies, variable selection methods are needed to identify the most responsive
genes in order to get a better interpretation of the results or to
conduct more specific experiments. These methods should be consistent
with the amount of signal in the data. For this purpose, we introduce a
novel selection strategy called minAS and also adapt other existing
strategies, such us Gamma approximation, resampling techniques, etc. All
of them are based on studying the distribution of statistics measuring
the importance of the variables in the model. These strategies have been
applied to the ASCA-genes analysis framework and more generally to
dimension reduction techniques as PCA. The performance of the different
strategies was evaluated using simulated data. The best performing
methods were then applied on an experimental dataset containing the
transcriptomic profiles of human embryonic stem cells cultured under
different oxygen concentrations. The ability of the methods to extract
relevant biological information from the data is discussed. (C) 2011
Elsevier B.V. All rights reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Dimension reduction techniques are used to explore genomic data. Due to
the large number of variables (genes) included in this kind of studies, variable selection methods are needed to identify the most responsive
genes in order to get a better interpretation of the results or to
conduct more specific experiments. These methods should be consistent
with the amount of signal in the data. For this purpose, we introduce a
novel selection strategy called minAS and also adapt other existing
strategies, such us Gamma approximation, resampling techniques, etc. All
of them are based on studying the distribution of statistics measuring
the importance of the variables in the model. These strategies have been
applied to the ASCA-genes analysis framework and more generally to
dimension reduction techniques as PCA. The performance of the different
strategies was evaluated using simulated data. The best performing
methods were then applied on an experimental dataset containing the
transcriptomic profiles of human embryonic stem cells cultured under
different oxygen concentrations. The ability of the methods to extract
relevant biological information from the data is discussed. (C) 2011
Elsevier B.V. All rights reserved.
the large number of variables (genes) included in this kind of studies, variable selection methods are needed to identify the most responsive
genes in order to get a better interpretation of the results or to
conduct more specific experiments. These methods should be consistent
with the amount of signal in the data. For this purpose, we introduce a
novel selection strategy called minAS and also adapt other existing
strategies, such us Gamma approximation, resampling techniques, etc. All
of them are based on studying the distribution of statistics measuring
the importance of the variables in the model. These strategies have been
applied to the ASCA-genes analysis framework and more generally to
dimension reduction techniques as PCA. The performance of the different
strategies was evaluated using simulated data. The best performing
methods were then applied on an experimental dataset containing the
transcriptomic profiles of human embryonic stem cells cultured under
different oxygen concentrations. The ability of the methods to extract
relevant biological information from the data is discussed. (C) 2011
Elsevier B.V. All rights reserved.
2011
39.
Yung, S.; Ledran, M.; Moreno-Gimeno, I.; Conesa, A.; Montaner, D.; Dopazo, J.; Dimmick, I.; Slater, N. J.; Marenah, L.; Real, P. J.; Paraskevopoulou, I.; Bisbal, V.; Burks, D.; Santibanez-Koref, M.; Moreno, R.; Mountford, J.; Menendez, P.; Armstrong, L.; Lako, M.
In: HUMAN MOLECULAR GENETICS, vol. 20, no. 24, pp. 4932-4946, 2011, ISSN: 0964-6906.
@article{ISI:000297242100015,
title = {Large-scale transcriptional profiling and functional assays reveal
important roles for Rho-GTPase signalling and SCL during haematopoietic
differentiation of human embryonic stem cells},
author = { S. Yung and M. Ledran and I. Moreno-Gimeno and A. Conesa and D. Montaner and J. Dopazo and I. Dimmick and N. J. Slater and L. Marenah and P. J. Real and I. Paraskevopoulou and V. Bisbal and D. Burks and M. Santibanez-Koref and R. Moreno and J. Mountford and P. Menendez and L. Armstrong and M. Lako},
url = {http://dx.doi.org/10.1093/hmg/ddr431},
doi = {10.1093/hmg/ddr431},
issn = {0964-6906},
year = {2011},
date = {2011-12-01},
journal = {HUMAN MOLECULAR GENETICS},
volume = {20},
number = {24},
pages = {4932-4946},
abstract = {Understanding the transcriptional cues that direct differentiation of
human embryonic stem cells (hESCs) and human-induced pluripotent stem
cells to defined and functional cell types is essential for future
clinical applications. In this study, we have compared transcriptional
profiles of haematopoietic progenitors derived from hESCs at various
developmental stages of a feeder-and serum-free differentiation method
and show that the largest transcriptional changes occur during the first
4 days of differentiation. Data mining on the basis of molecular
function revealed Rho-GTPase signalling as a key regulator of
differentiation. Inhibition of this pathway resulted in a significant
reduction in the numbers of emerging haematopoietic progenitors
throughout the differentiation window, thereby uncovering a previously
unappreciated role for Rho-GTPase signalling during human haematopoietic
development. Our analysis indicated that SCL was the 11th most
upregulated transcript during the first 4 days of the hESC
differentiation process. Overexpression of SCL in hESCs promoted
differentiation to meso-endodermal lineages, the emergence of
haematopoietic and erythro-megakaryocytic progenitors and accelerated
erythroid differentiation. Importantly, intrasplenic transplantation of
SCL-overexpressing hESC-derived haematopoietic cells enhanced recovery
from induced acute anaemia without significant cell engraftment, suggesting a paracrine-mediated effect.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Understanding the transcriptional cues that direct differentiation of
human embryonic stem cells (hESCs) and human-induced pluripotent stem
cells to defined and functional cell types is essential for future
clinical applications. In this study, we have compared transcriptional
profiles of haematopoietic progenitors derived from hESCs at various
developmental stages of a feeder-and serum-free differentiation method
and show that the largest transcriptional changes occur during the first
4 days of differentiation. Data mining on the basis of molecular
function revealed Rho-GTPase signalling as a key regulator of
differentiation. Inhibition of this pathway resulted in a significant
reduction in the numbers of emerging haematopoietic progenitors
throughout the differentiation window, thereby uncovering a previously
unappreciated role for Rho-GTPase signalling during human haematopoietic
development. Our analysis indicated that SCL was the 11th most
upregulated transcript during the first 4 days of the hESC
differentiation process. Overexpression of SCL in hESCs promoted
differentiation to meso-endodermal lineages, the emergence of
haematopoietic and erythro-megakaryocytic progenitors and accelerated
erythroid differentiation. Importantly, intrasplenic transplantation of
SCL-overexpressing hESC-derived haematopoietic cells enhanced recovery
from induced acute anaemia without significant cell engraftment, suggesting a paracrine-mediated effect.
human embryonic stem cells (hESCs) and human-induced pluripotent stem
cells to defined and functional cell types is essential for future
clinical applications. In this study, we have compared transcriptional
profiles of haematopoietic progenitors derived from hESCs at various
developmental stages of a feeder-and serum-free differentiation method
and show that the largest transcriptional changes occur during the first
4 days of differentiation. Data mining on the basis of molecular
function revealed Rho-GTPase signalling as a key regulator of
differentiation. Inhibition of this pathway resulted in a significant
reduction in the numbers of emerging haematopoietic progenitors
throughout the differentiation window, thereby uncovering a previously
unappreciated role for Rho-GTPase signalling during human haematopoietic
development. Our analysis indicated that SCL was the 11th most
upregulated transcript during the first 4 days of the hESC
differentiation process. Overexpression of SCL in hESCs promoted
differentiation to meso-endodermal lineages, the emergence of
haematopoietic and erythro-megakaryocytic progenitors and accelerated
erythroid differentiation. Importantly, intrasplenic transplantation of
SCL-overexpressing hESC-derived haematopoietic cells enhanced recovery
from induced acute anaemia without significant cell engraftment, suggesting a paracrine-mediated effect.
38.
Tarazona, S.; Garcia-Alcalde, F.; Dopazo, J.; Ferrer, A.; Conesa, A.
Differential expression in RNA-seq: A matter of depth Journal Article
In: GENOME RESEARCH, vol. 21, no. 12, pp. 2213-2223, 2011, ISSN: 1088-9051.
@article{ISI:000297918600020,
title = {Differential expression in RNA-seq: A matter of depth},
author = { S. Tarazona and F. Garcia-Alcalde and J. Dopazo and A. Ferrer and A. Conesa},
url = {http://dx.doi.org/10.1101/gr.124321.111},
doi = {10.1101/gr.124321.111},
issn = {1088-9051},
year = {2011},
date = {2011-12-01},
journal = {GENOME RESEARCH},
volume = {21},
number = {12},
pages = {2213-2223},
abstract = {Next-generation sequencing (NGS) technologies are revolutionizing genome
research, and in particular, their application to transcriptomics
(RNA-seq) is increasingly being used for gene expression profiling as a
replacement for microarrays. However, the properties of RNA-seq data
have not been yet fully established, and additional research is needed
for understanding how these data respond to differential expression
analysis. In this work, we set out to gain insights into the
characteristics of RNA-seq data analysis by studying an important
parameter of this technology: the sequencing depth. We have analyzed how
sequencing depth affects the detection of transcripts and their
identification as differentially expressed, looking at aspects such as
transcript biotype, length, expression level, and fold-change. We have
evaluated different algorithms available for the analysis of RNA-seq and
proposed a novel approach-NOISeq-that differs from existing methods in
that it is data-adaptive and nonparametric. Our results reveal that most
existing methodologies suffer from a strong dependency on sequencing
depth for their differential expression calls and that this results in a
considerable number of false positives that increases as the number of
reads grows. In contrast, our proposed method models the noise
distribution from the actual data, can therefore better adapt to the
size of the data set, and is more effective in controlling the rate of
false discoveries. This work discusses the true potential of RNA-seq for
studying regulation at low expression ranges, the noise within RNA-seq
data, and the issue of replication.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Next-generation sequencing (NGS) technologies are revolutionizing genome
research, and in particular, their application to transcriptomics
(RNA-seq) is increasingly being used for gene expression profiling as a
replacement for microarrays. However, the properties of RNA-seq data
have not been yet fully established, and additional research is needed
for understanding how these data respond to differential expression
analysis. In this work, we set out to gain insights into the
characteristics of RNA-seq data analysis by studying an important
parameter of this technology: the sequencing depth. We have analyzed how
sequencing depth affects the detection of transcripts and their
identification as differentially expressed, looking at aspects such as
transcript biotype, length, expression level, and fold-change. We have
evaluated different algorithms available for the analysis of RNA-seq and
proposed a novel approach-NOISeq-that differs from existing methods in
that it is data-adaptive and nonparametric. Our results reveal that most
existing methodologies suffer from a strong dependency on sequencing
depth for their differential expression calls and that this results in a
considerable number of false positives that increases as the number of
reads grows. In contrast, our proposed method models the noise
distribution from the actual data, can therefore better adapt to the
size of the data set, and is more effective in controlling the rate of
false discoveries. This work discusses the true potential of RNA-seq for
studying regulation at low expression ranges, the noise within RNA-seq
data, and the issue of replication.
research, and in particular, their application to transcriptomics
(RNA-seq) is increasingly being used for gene expression profiling as a
replacement for microarrays. However, the properties of RNA-seq data
have not been yet fully established, and additional research is needed
for understanding how these data respond to differential expression
analysis. In this work, we set out to gain insights into the
characteristics of RNA-seq data analysis by studying an important
parameter of this technology: the sequencing depth. We have analyzed how
sequencing depth affects the detection of transcripts and their
identification as differentially expressed, looking at aspects such as
transcript biotype, length, expression level, and fold-change. We have
evaluated different algorithms available for the analysis of RNA-seq and
proposed a novel approach-NOISeq-that differs from existing methods in
that it is data-adaptive and nonparametric. Our results reveal that most
existing methodologies suffer from a strong dependency on sequencing
depth for their differential expression calls and that this results in a
considerable number of false positives that increases as the number of
reads grows. In contrast, our proposed method models the noise
distribution from the actual data, can therefore better adapt to the
size of the data set, and is more effective in controlling the rate of
false discoveries. This work discusses the true potential of RNA-seq for
studying regulation at low expression ranges, the noise within RNA-seq
data, and the issue of replication.
37.
Khalaf, A. A.; Gmitter, Jr.; Conesa, A.; Dopazo, J.; Moore, G. A.
Fortunella margarita Transcriptional Reprogramming Triggered by Xanthomonas citri subsp citri Journal Article
In: BMC PLANT BIOLOGY, vol. 11, 2011, ISSN: 1471-2229.
@article{ISI:000297983800001,
title = {Fortunella margarita Transcriptional Reprogramming Triggered by
Xanthomonas citri subsp citri},
author = { A. A. Khalaf and Jr. Gmitter and A. Conesa and J. Dopazo and G. A. Moore},
url = {http://dx.doi.org/10.1186/1471-2229-11-159},
doi = {10.1186/1471-2229-11-159},
issn = {1471-2229},
year = {2011},
date = {2011-11-01},
journal = {BMC PLANT BIOLOGY},
volume = {11},
abstract = {Background: Citrus canker disease caused by the bacterial pathogen
Xanthomonas citri subsp. citri (Xcc) has become endemic in areas where
high temperature, rain, humidity, and windy conditions provide a
favourable environment for the dissemination of the bacterium. Xcc is
pathogenic on many commercial citrus varieties but appears to elicit an
incompatible reaction on the citrus relative Fortunella margarita Swing
(kumquat), in the form of a very distinct delayed necrotic response. We
have developed subtractive libraries enriched in sequences expressed in
kumquat leaves during both early and late stages of the disease. The
isolated differentially expressed transcripts were subsequently
sequenced. Our results demonstrate how the use of microarray expression
profiling can help assign roles to previously uncharacterized genes and
elucidate plant pathogenesis-response related mechanisms. This can be
considered to be a case study in a citrus relative where high throughput
technologies were utilized to understand defence mechanisms in
Fortunella and citrus at the molecular level.
Results: cDNAs from sequenced kumquat libraries (ESTs) made from
subtracted RNA populations, healthy vs. infected, were used to make this
microarray. Of 2054 selected genes on a customized array, 317 were
differentially expressed (P < 0.05) in Xcc challenged kumquat plants
compared to mock-inoculated ones. This study identified components of
the incompatible interaction such as reactive oxygen species (ROS) and
programmed cell death (PCD). Common defence mechanisms and a number of
resistance genes were also identified. In addition, there were a
considerable number of differentially regulated genes that had no
homologues in the databases. This could be an indication of either a
specialized set of genes employed by kumquat in response to canker
disease or new defence mechanisms in citrus.
Conclusion: Functional categorization of kumquat Xcc-responsive genes
revealed an enhanced defence-related metabolism as well as a number of
resistant response-specific genes in the kumquat transcriptome in
response to Xcc inoculation. Gene expression profile(s) were analyzed to
assemble a comprehensive and inclusive image of the molecular
interaction in the kumquat/Xcc system. This was done in order to
elucidate molecular mechanisms associated with the development of the
hypersensitive response phenotype in kumquat leaves. These data will be
used to perform comparisons among citrus species to evaluate means to
enhance the host immune responses against bacterial diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Citrus canker disease caused by the bacterial pathogen
Xanthomonas citri subsp. citri (Xcc) has become endemic in areas where
high temperature, rain, humidity, and windy conditions provide a
favourable environment for the dissemination of the bacterium. Xcc is
pathogenic on many commercial citrus varieties but appears to elicit an
incompatible reaction on the citrus relative Fortunella margarita Swing
(kumquat), in the form of a very distinct delayed necrotic response. We
have developed subtractive libraries enriched in sequences expressed in
kumquat leaves during both early and late stages of the disease. The
isolated differentially expressed transcripts were subsequently
sequenced. Our results demonstrate how the use of microarray expression
profiling can help assign roles to previously uncharacterized genes and
elucidate plant pathogenesis-response related mechanisms. This can be
considered to be a case study in a citrus relative where high throughput
technologies were utilized to understand defence mechanisms in
Fortunella and citrus at the molecular level.
Results: cDNAs from sequenced kumquat libraries (ESTs) made from
subtracted RNA populations, healthy vs. infected, were used to make this
microarray. Of 2054 selected genes on a customized array, 317 were
differentially expressed (P < 0.05) in Xcc challenged kumquat plants
compared to mock-inoculated ones. This study identified components of
the incompatible interaction such as reactive oxygen species (ROS) and
programmed cell death (PCD). Common defence mechanisms and a number of
resistance genes were also identified. In addition, there were a
considerable number of differentially regulated genes that had no
homologues in the databases. This could be an indication of either a
specialized set of genes employed by kumquat in response to canker
disease or new defence mechanisms in citrus.
Conclusion: Functional categorization of kumquat Xcc-responsive genes
revealed an enhanced defence-related metabolism as well as a number of
resistant response-specific genes in the kumquat transcriptome in
response to Xcc inoculation. Gene expression profile(s) were analyzed to
assemble a comprehensive and inclusive image of the molecular
interaction in the kumquat/Xcc system. This was done in order to
elucidate molecular mechanisms associated with the development of the
hypersensitive response phenotype in kumquat leaves. These data will be
used to perform comparisons among citrus species to evaluate means to
enhance the host immune responses against bacterial diseases.
Xanthomonas citri subsp. citri (Xcc) has become endemic in areas where
high temperature, rain, humidity, and windy conditions provide a
favourable environment for the dissemination of the bacterium. Xcc is
pathogenic on many commercial citrus varieties but appears to elicit an
incompatible reaction on the citrus relative Fortunella margarita Swing
(kumquat), in the form of a very distinct delayed necrotic response. We
have developed subtractive libraries enriched in sequences expressed in
kumquat leaves during both early and late stages of the disease. The
isolated differentially expressed transcripts were subsequently
sequenced. Our results demonstrate how the use of microarray expression
profiling can help assign roles to previously uncharacterized genes and
elucidate plant pathogenesis-response related mechanisms. This can be
considered to be a case study in a citrus relative where high throughput
technologies were utilized to understand defence mechanisms in
Fortunella and citrus at the molecular level.
Results: cDNAs from sequenced kumquat libraries (ESTs) made from
subtracted RNA populations, healthy vs. infected, were used to make this
microarray. Of 2054 selected genes on a customized array, 317 were
differentially expressed (P < 0.05) in Xcc challenged kumquat plants
compared to mock-inoculated ones. This study identified components of
the incompatible interaction such as reactive oxygen species (ROS) and
programmed cell death (PCD). Common defence mechanisms and a number of
resistance genes were also identified. In addition, there were a
considerable number of differentially regulated genes that had no
homologues in the databases. This could be an indication of either a
specialized set of genes employed by kumquat in response to canker
disease or new defence mechanisms in citrus.
Conclusion: Functional categorization of kumquat Xcc-responsive genes
revealed an enhanced defence-related metabolism as well as a number of
resistant response-specific genes in the kumquat transcriptome in
response to Xcc inoculation. Gene expression profile(s) were analyzed to
assemble a comprehensive and inclusive image of the molecular
interaction in the kumquat/Xcc system. This was done in order to
elucidate molecular mechanisms associated with the development of the
hypersensitive response phenotype in kumquat leaves. These data will be
used to perform comparisons among citrus species to evaluate means to
enhance the host immune responses against bacterial diseases.
36.
Durban, J.; Juarez, P.; Angulo, Y.; Lomonte, B.; Flores-Diaz, M.; Alape-Giron, A.; Sasa, M.; Sanz, L.; Gutierrez, J. M.; Dopazo, J.; Conesa, A.; Calvete, J. J.
Profiling the venom gland transcriptomes of Costa Rican snakes by 454 pyrosequencing Journal Article
In: BMC GENOMICS, vol. 12, 2011, ISSN: 1471-2164.
@article{ISI:000292249800002,
title = {Profiling the venom gland transcriptomes of Costa Rican snakes by 454
pyrosequencing},
author = { J. Durban and P. Juarez and Y. Angulo and B. Lomonte and M. Flores-Diaz and A. Alape-Giron and M. Sasa and L. Sanz and J. M. Gutierrez and J. Dopazo and A. Conesa and J. J. Calvete},
url = {http://dx.doi.org/10.1186/1471-2164-12-259},
doi = {10.1186/1471-2164-12-259},
issn = {1471-2164},
year = {2011},
date = {2011-05-01},
journal = {BMC GENOMICS},
volume = {12},
abstract = {Background: A long term research goal of venomics, of applied importance
for improving current antivenom therapy, but also for drug discovery, is
to understand the pharmacological potential of venoms. Individually or
combined, proteomic and transcriptomic studies have demonstrated their
feasibility to explore in depth the molecular diversity of venoms. In
the absence of genome sequence, transcriptomes represent also valuable
searchable databases for proteomic projects.
Results: The venom gland transcriptomes of 8 Costa Rican taxa from 5
genera (Crotalus, Bothrops, Atropoides, Cerrophidion, and Bothriechis)
of pitvipers were investigated using high-throughput 454 pyrosequencing.
100,394 out of 330,010 masked reads produced significant hits in the
available databases. 5.165,220 nucleotides (8.27%) were masked by
RepeatMasker, the vast majority of which corresponding to class I
(retroelements) and class II (DNA transposons) mobile elements. BLAST
hits included 79,991 matches to entries of the taxonomic suborder
Serpentes, of which 62,433 displayed similarity to documented venom
proteins. Strong discrepancies between the transcriptome-computed and
the proteome-gathered toxin compositions were obvious at first sight.
Although the reasons underlaying this discrepancy are elusive, since no
clear trend within or between species is apparent, the data indicate
that individual mRNA species may be translationally controlled in a
species-dependent manner. The minimum number of genes from each toxin
family transcribed into the venom gland transcriptome of each species
was calculated from multiple alignments of reads matched to a
full-length reference sequence of each toxin family. Reads encoding ORF
regions of Kazal-type inhibitor-like proteins were uniquely found in
Bothriechis schlegelii and B. lateralis transcriptomes, suggesting a
genus-specific recruitment event during the early-Middle Miocene. A
transcriptome-based cladogram supports the large divergence between A.
mexicanus and A. picadoi, and a closer kinship between A. mexicanus and
C. godmani.
Conclusions: Our comparative next-generation sequencing (NGS) analysis
reveals taxon-specific trends governing the formulation of the venom
arsenal. Knowledge of the venom proteome provides hints on the
translation efficiency of toxin-coding transcripts, contributing thereby
to a more accurate interpretation of the transcriptome. The application
of NGS to the analysis of snake venom transcriptomes, may represent the
tool for opening the door to systems venomics.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: A long term research goal of venomics, of applied importance
for improving current antivenom therapy, but also for drug discovery, is
to understand the pharmacological potential of venoms. Individually or
combined, proteomic and transcriptomic studies have demonstrated their
feasibility to explore in depth the molecular diversity of venoms. In
the absence of genome sequence, transcriptomes represent also valuable
searchable databases for proteomic projects.
Results: The venom gland transcriptomes of 8 Costa Rican taxa from 5
genera (Crotalus, Bothrops, Atropoides, Cerrophidion, and Bothriechis)
of pitvipers were investigated using high-throughput 454 pyrosequencing.
100,394 out of 330,010 masked reads produced significant hits in the
available databases. 5.165,220 nucleotides (8.27%) were masked by
RepeatMasker, the vast majority of which corresponding to class I
(retroelements) and class II (DNA transposons) mobile elements. BLAST
hits included 79,991 matches to entries of the taxonomic suborder
Serpentes, of which 62,433 displayed similarity to documented venom
proteins. Strong discrepancies between the transcriptome-computed and
the proteome-gathered toxin compositions were obvious at first sight.
Although the reasons underlaying this discrepancy are elusive, since no
clear trend within or between species is apparent, the data indicate
that individual mRNA species may be translationally controlled in a
species-dependent manner. The minimum number of genes from each toxin
family transcribed into the venom gland transcriptome of each species
was calculated from multiple alignments of reads matched to a
full-length reference sequence of each toxin family. Reads encoding ORF
regions of Kazal-type inhibitor-like proteins were uniquely found in
Bothriechis schlegelii and B. lateralis transcriptomes, suggesting a
genus-specific recruitment event during the early-Middle Miocene. A
transcriptome-based cladogram supports the large divergence between A.
mexicanus and A. picadoi, and a closer kinship between A. mexicanus and
C. godmani.
Conclusions: Our comparative next-generation sequencing (NGS) analysis
reveals taxon-specific trends governing the formulation of the venom
arsenal. Knowledge of the venom proteome provides hints on the
translation efficiency of toxin-coding transcripts, contributing thereby
to a more accurate interpretation of the transcriptome. The application
of NGS to the analysis of snake venom transcriptomes, may represent the
tool for opening the door to systems venomics.
for improving current antivenom therapy, but also for drug discovery, is
to understand the pharmacological potential of venoms. Individually or
combined, proteomic and transcriptomic studies have demonstrated their
feasibility to explore in depth the molecular diversity of venoms. In
the absence of genome sequence, transcriptomes represent also valuable
searchable databases for proteomic projects.
Results: The venom gland transcriptomes of 8 Costa Rican taxa from 5
genera (Crotalus, Bothrops, Atropoides, Cerrophidion, and Bothriechis)
of pitvipers were investigated using high-throughput 454 pyrosequencing.
100,394 out of 330,010 masked reads produced significant hits in the
available databases. 5.165,220 nucleotides (8.27%) were masked by
RepeatMasker, the vast majority of which corresponding to class I
(retroelements) and class II (DNA transposons) mobile elements. BLAST
hits included 79,991 matches to entries of the taxonomic suborder
Serpentes, of which 62,433 displayed similarity to documented venom
proteins. Strong discrepancies between the transcriptome-computed and
the proteome-gathered toxin compositions were obvious at first sight.
Although the reasons underlaying this discrepancy are elusive, since no
clear trend within or between species is apparent, the data indicate
that individual mRNA species may be translationally controlled in a
species-dependent manner. The minimum number of genes from each toxin
family transcribed into the venom gland transcriptome of each species
was calculated from multiple alignments of reads matched to a
full-length reference sequence of each toxin family. Reads encoding ORF
regions of Kazal-type inhibitor-like proteins were uniquely found in
Bothriechis schlegelii and B. lateralis transcriptomes, suggesting a
genus-specific recruitment event during the early-Middle Miocene. A
transcriptome-based cladogram supports the large divergence between A.
mexicanus and A. picadoi, and a closer kinship between A. mexicanus and
C. godmani.
Conclusions: Our comparative next-generation sequencing (NGS) analysis
reveals taxon-specific trends governing the formulation of the venom
arsenal. Knowledge of the venom proteome provides hints on the
translation efficiency of toxin-coding transcripts, contributing thereby
to a more accurate interpretation of the transcriptome. The application
of NGS to the analysis of snake venom transcriptomes, may represent the
tool for opening the door to systems venomics.
35.
Goetz, S.; Arnold, R.; Sebastian-Leon, P.; Martin-Rodriguez, S.; Tischler, P.; Jehl, M.; Dopazo, J.; Rattei, T.; Conesa, A.
B2G-FAR, a species-centered GO annotation repository Journal Article
In: BIOINFORMATICS, vol. 27, no. 7, pp. 919-924, 2011, ISSN: 1367-4803.
@article{ISI:000289162000005,
title = {B2G-FAR, a species-centered GO annotation repository},
author = { S. Goetz and R. Arnold and P. Sebastian-Leon and S. Martin-Rodriguez and P. Tischler and M. Jehl and J. Dopazo and T. Rattei and A. Conesa},
url = {http://dx.doi.org/10.1093/bioinformatics/btr059},
doi = {10.1093/bioinformatics/btr059},
issn = {1367-4803},
year = {2011},
date = {2011-04-01},
journal = {BIOINFORMATICS},
volume = {27},
number = {7},
pages = {919-924},
abstract = {Motivation: Functional genomics research has expanded enormously in the
last decade thanks to the cost reduction in high-throughput technologies
and the development of computational tools that generate, standardize
and share information on gene and protein function such as the Gene
Ontology ( GO). Nevertheless, many biologists, especially working with
non-model organisms, still suffer from non-existing or low-coverage
functional annotation, or simply struggle retrieving, summarizing and
querying these data.
Results: The Blast2GO Functional Annotation Repository (B2G-FAR) is a
bioinformatics resource envisaged to provide functional information for
otherwise uncharacterized sequence data and offers data mining tools to
analyze a larger repertoire of species than currently available. This
new annotation resource has been created by applying the Blast2GO
functional annotation engine in a strongly high-throughput manner to the
entire space of public available sequences. The resulting repository
contains GO term predictions for over 13.2 million non-redundant protein
sequences based on BLAST search alignments from the SIMAP database. We
generated GO annotation for approximately 150 000 different taxa making
available 2000 species with the highest coverage through B2G-FAR. A
second section within B2G-FAR holds functional annotations for 17
non-model organism Affymetrix GeneChips.
Conclusions: B2G-FAR provides easy access to exhaustive functional
annotation for 2000 species offering a good balance between quality and
quantity, thereby supporting functional genomics research especially in
the case of non-model organisms.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Motivation: Functional genomics research has expanded enormously in the
last decade thanks to the cost reduction in high-throughput technologies
and the development of computational tools that generate, standardize
and share information on gene and protein function such as the Gene
Ontology ( GO). Nevertheless, many biologists, especially working with
non-model organisms, still suffer from non-existing or low-coverage
functional annotation, or simply struggle retrieving, summarizing and
querying these data.
Results: The Blast2GO Functional Annotation Repository (B2G-FAR) is a
bioinformatics resource envisaged to provide functional information for
otherwise uncharacterized sequence data and offers data mining tools to
analyze a larger repertoire of species than currently available. This
new annotation resource has been created by applying the Blast2GO
functional annotation engine in a strongly high-throughput manner to the
entire space of public available sequences. The resulting repository
contains GO term predictions for over 13.2 million non-redundant protein
sequences based on BLAST search alignments from the SIMAP database. We
generated GO annotation for approximately 150 000 different taxa making
available 2000 species with the highest coverage through B2G-FAR. A
second section within B2G-FAR holds functional annotations for 17
non-model organism Affymetrix GeneChips.
Conclusions: B2G-FAR provides easy access to exhaustive functional
annotation for 2000 species offering a good balance between quality and
quantity, thereby supporting functional genomics research especially in
the case of non-model organisms.
last decade thanks to the cost reduction in high-throughput technologies
and the development of computational tools that generate, standardize
and share information on gene and protein function such as the Gene
Ontology ( GO). Nevertheless, many biologists, especially working with
non-model organisms, still suffer from non-existing or low-coverage
functional annotation, or simply struggle retrieving, summarizing and
querying these data.
Results: The Blast2GO Functional Annotation Repository (B2G-FAR) is a
bioinformatics resource envisaged to provide functional information for
otherwise uncharacterized sequence data and offers data mining tools to
analyze a larger repertoire of species than currently available. This
new annotation resource has been created by applying the Blast2GO
functional annotation engine in a strongly high-throughput manner to the
entire space of public available sequences. The resulting repository
contains GO term predictions for over 13.2 million non-redundant protein
sequences based on BLAST search alignments from the SIMAP database. We
generated GO annotation for approximately 150 000 different taxa making
available 2000 species with the highest coverage through B2G-FAR. A
second section within B2G-FAR holds functional annotations for 17
non-model organism Affymetrix GeneChips.
Conclusions: B2G-FAR provides easy access to exhaustive functional
annotation for 2000 species offering a good balance between quality and
quantity, thereby supporting functional genomics research especially in
the case of non-model organisms.
34.
Garrido-Gomez, T.; Dominguez, F.; Lopez, J. Antonio; Camafeita, E.; Quinonero, A.; Martinez-Conejero, J. Antonio; Pellicer, A.; Conesa, A.; Simon, C.
Modeling Human Endometrial Decidualization from the Interaction between Proteome and Secretome Journal Article
In: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, vol. 96, no. 3, pp. 706-716, 2011, ISSN: 0021-972X.
@article{ISI:000288020600040,
title = {Modeling Human Endometrial Decidualization from the Interaction between
Proteome and Secretome},
author = { T. Garrido-Gomez and F. Dominguez and J. Antonio Lopez and E. Camafeita and A. Quinonero and J. Antonio Martinez-Conejero and A. Pellicer and A. Conesa and C. Simon},
url = {http://dx.doi.org/10.1210/jc.2010-1825},
doi = {10.1210/jc.2010-1825},
issn = {0021-972X},
year = {2011},
date = {2011-03-01},
journal = {JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM},
volume = {96},
number = {3},
pages = {706-716},
abstract = {Context: Decidualization of the human endometrium, which involves
morphological and biochemical modifications of the endometrial stromal
cells (ESCs), is a prerequisite for adequate trophoblast invasion and
placenta formation.
Objective: This study aims to investigate the proteome and secretome of
in vitro decidualized ESCs. These data were combined with published
genomic information and integrated to model the human decidualization
interactome.
Design: Prospective experimental case-control study.
Setting: A private research foundation.
Patients: Sixteen healthy volunteer ovum donors.
Intervention: Endometrial samples were obtained, and ESCs were isolated
and decidualized in vitro.
Main Outcome Measures: Two-dimensional difference in-gel
electrophoresis, matrix-assisted laser
desorption/ionization-time-of-flight mass spectrometry, Western blot, human protein cytokine array, ELISA, and bioinformatics analysis were
performed.
Results: The proteomic analysis revealed 60 differentially expressed
proteins (36 over-and 24 underexpressed) in decidualized versus control
ESCs, including known decidualization markers (cathepsin B) and new
biomarkers (transglutaminase 2, peroxiredoxin 4, and the ACTB protein).
In the secretomic analysis, a total of 13 secreted proteins (11 up-and 2
down-regulated) were identified, including well-recognized markers (IGF
binding protein-1 and prolactin) and novel ones (myeloid progenitor
inhibitory factor-1 and platelet endothelial cell adhesion molecule-1).
These proteome/secretome profiles have been integrated into a
decidualization interactome model.
Conclusions: Proteomic and secretomic have been used as hypothesis-free
approaches together with complex bioinformatics to model the human
decidual interactome for the first time. We confirm previous knowledge, describe new molecules, and we have built up a model for human in vitro
decidualization as invaluable tool for the diagnosis, therapy, and
interpretation of biological phenomena. (J Clin Endocrinol Metab 96:
706-716, 2011)},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Context: Decidualization of the human endometrium, which involves
morphological and biochemical modifications of the endometrial stromal
cells (ESCs), is a prerequisite for adequate trophoblast invasion and
placenta formation.
Objective: This study aims to investigate the proteome and secretome of
in vitro decidualized ESCs. These data were combined with published
genomic information and integrated to model the human decidualization
interactome.
Design: Prospective experimental case-control study.
Setting: A private research foundation.
Patients: Sixteen healthy volunteer ovum donors.
Intervention: Endometrial samples were obtained, and ESCs were isolated
and decidualized in vitro.
Main Outcome Measures: Two-dimensional difference in-gel
electrophoresis, matrix-assisted laser
desorption/ionization-time-of-flight mass spectrometry, Western blot, human protein cytokine array, ELISA, and bioinformatics analysis were
performed.
Results: The proteomic analysis revealed 60 differentially expressed
proteins (36 over-and 24 underexpressed) in decidualized versus control
ESCs, including known decidualization markers (cathepsin B) and new
biomarkers (transglutaminase 2, peroxiredoxin 4, and the ACTB protein).
In the secretomic analysis, a total of 13 secreted proteins (11 up-and 2
down-regulated) were identified, including well-recognized markers (IGF
binding protein-1 and prolactin) and novel ones (myeloid progenitor
inhibitory factor-1 and platelet endothelial cell adhesion molecule-1).
These proteome/secretome profiles have been integrated into a
decidualization interactome model.
Conclusions: Proteomic and secretomic have been used as hypothesis-free
approaches together with complex bioinformatics to model the human
decidual interactome for the first time. We confirm previous knowledge, describe new molecules, and we have built up a model for human in vitro
decidualization as invaluable tool for the diagnosis, therapy, and
interpretation of biological phenomena. (J Clin Endocrinol Metab 96:
706-716, 2011)
morphological and biochemical modifications of the endometrial stromal
cells (ESCs), is a prerequisite for adequate trophoblast invasion and
placenta formation.
Objective: This study aims to investigate the proteome and secretome of
in vitro decidualized ESCs. These data were combined with published
genomic information and integrated to model the human decidualization
interactome.
Design: Prospective experimental case-control study.
Setting: A private research foundation.
Patients: Sixteen healthy volunteer ovum donors.
Intervention: Endometrial samples were obtained, and ESCs were isolated
and decidualized in vitro.
Main Outcome Measures: Two-dimensional difference in-gel
electrophoresis, matrix-assisted laser
desorption/ionization-time-of-flight mass spectrometry, Western blot, human protein cytokine array, ELISA, and bioinformatics analysis were
performed.
Results: The proteomic analysis revealed 60 differentially expressed
proteins (36 over-and 24 underexpressed) in decidualized versus control
ESCs, including known decidualization markers (cathepsin B) and new
biomarkers (transglutaminase 2, peroxiredoxin 4, and the ACTB protein).
In the secretomic analysis, a total of 13 secreted proteins (11 up-and 2
down-regulated) were identified, including well-recognized markers (IGF
binding protein-1 and prolactin) and novel ones (myeloid progenitor
inhibitory factor-1 and platelet endothelial cell adhesion molecule-1).
These proteome/secretome profiles have been integrated into a
decidualization interactome model.
Conclusions: Proteomic and secretomic have been used as hypothesis-free
approaches together with complex bioinformatics to model the human
decidual interactome for the first time. We confirm previous knowledge, describe new molecules, and we have built up a model for human in vitro
decidualization as invaluable tool for the diagnosis, therapy, and
interpretation of biological phenomena. (J Clin Endocrinol Metab 96:
706-716, 2011)
33.
Garcia-Alcalde, F.; Garcia-Lopez, F.; Dopazo, J.; Conesa, A.
Paintomics: a web based tool for the joint visualization of transcriptomics and metabolomics data Journal Article
In: BIOINFORMATICS, vol. 27, no. 1, pp. 137-139, 2011, ISSN: 1367-4803.
@article{ISI:000285626300021,
title = {Paintomics: a web based tool for the joint visualization of
transcriptomics and metabolomics data},
author = { F. Garcia-Alcalde and F. Garcia-Lopez and J. Dopazo and A. Conesa},
url = {http://dx.doi.org/10.1093/bioinformatics/btq594},
doi = {10.1093/bioinformatics/btq594},
issn = {1367-4803},
year = {2011},
date = {2011-01-01},
journal = {BIOINFORMATICS},
volume = {27},
number = {1},
pages = {137-139},
abstract = {Motivation: The development of the omics technologies such as
transcriptomics, proteomics and metabolomics has made possible the
realization of systems biology studies where biological systems are
interrogated at different levels of biochemical activity (gene
expression, protein activity and/or metabolite concentration). An
effective approach to the analysis of these complex datasets is the
joined visualization of the disparate biomolecular data on the framework
of known biological pathways.
Results: We have developed the Paintomics web server as an easy-to-use
bioinformatics resource that facilitates the integrated visual analysis
of experiments where transcriptomics and metabolomics data have been
measured on different conditions for the same samples. Basically, Paintomics takes complete transcriptomics and metabolomics datasets, together with lists of significant gene or metabolite changes, and
paints this information on KEGG pathway maps.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Motivation: The development of the omics technologies such as
transcriptomics, proteomics and metabolomics has made possible the
realization of systems biology studies where biological systems are
interrogated at different levels of biochemical activity (gene
expression, protein activity and/or metabolite concentration). An
effective approach to the analysis of these complex datasets is the
joined visualization of the disparate biomolecular data on the framework
of known biological pathways.
Results: We have developed the Paintomics web server as an easy-to-use
bioinformatics resource that facilitates the integrated visual analysis
of experiments where transcriptomics and metabolomics data have been
measured on different conditions for the same samples. Basically, Paintomics takes complete transcriptomics and metabolomics datasets, together with lists of significant gene or metabolite changes, and
paints this information on KEGG pathway maps.
transcriptomics, proteomics and metabolomics has made possible the
realization of systems biology studies where biological systems are
interrogated at different levels of biochemical activity (gene
expression, protein activity and/or metabolite concentration). An
effective approach to the analysis of these complex datasets is the
joined visualization of the disparate biomolecular data on the framework
of known biological pathways.
Results: We have developed the Paintomics web server as an easy-to-use
bioinformatics resource that facilitates the integrated visual analysis
of experiments where transcriptomics and metabolomics data have been
measured on different conditions for the same samples. Basically, Paintomics takes complete transcriptomics and metabolomics datasets, together with lists of significant gene or metabolite changes, and
paints this information on KEGG pathway maps.
2010
32.
Conesa, A.; Prats-Montalban, J. M.; Tarazona, S.; Nueda, M. Jose; Ferrer, A.
A multiway approach to data integration in systems biology based on Tucker3 and N-PLS Journal Article
In: CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS, vol. 104, no. 1, SI, pp. 101-111, 2010, ISSN: 0169-7439.
@article{ISI:000284658300011,
title = {A multiway approach to data integration in systems biology based on
Tucker3 and N-PLS},
author = { A. Conesa and J. M. Prats-Montalban and S. Tarazona and M. Jose Nueda and A. Ferrer},
url = {http://dx.doi.org/10.1016/j.chemolab.2010.06.004},
doi = {10.1016/j.chemolab.2010.06.004},
issn = {0169-7439},
year = {2010},
date = {2010-11-01},
journal = {CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS},
volume = {104},
number = {1, SI},
pages = {101-111},
abstract = {This paper discusses the potential of multi-way projection methods for
analysing multifactorial data structures to identify underlying
components of variability that interconnect different blocks of omics
variables. We explore their suitability for explorative and variable
selection analysis of systems biology data where different types of
biological parameters are studied together. These methodologies were
applied to the integrative analysis of a functional genomics dataset
where transcriptomics, metabolomics and physiological data are
available. Our results show that multiway methods are suited to
accommodate multifactorial omics experiments and to analyse
relationships between different biochemical layers. Additionally, strategies are presented for variable selection in the context of omics
data and for interpreting results at the level of cellular pathways. (C)
2010 Elsevier B.V. All rights reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
This paper discusses the potential of multi-way projection methods for
analysing multifactorial data structures to identify underlying
components of variability that interconnect different blocks of omics
variables. We explore their suitability for explorative and variable
selection analysis of systems biology data where different types of
biological parameters are studied together. These methodologies were
applied to the integrative analysis of a functional genomics dataset
where transcriptomics, metabolomics and physiological data are
available. Our results show that multiway methods are suited to
accommodate multifactorial omics experiments and to analyse
relationships between different biochemical layers. Additionally, strategies are presented for variable selection in the context of omics
data and for interpreting results at the level of cellular pathways. (C)
2010 Elsevier B.V. All rights reserved.
analysing multifactorial data structures to identify underlying
components of variability that interconnect different blocks of omics
variables. We explore their suitability for explorative and variable
selection analysis of systems biology data where different types of
biological parameters are studied together. These methodologies were
applied to the integrative analysis of a functional genomics dataset
where transcriptomics, metabolomics and physiological data are
available. Our results show that multiway methods are suited to
accommodate multifactorial omics experiments and to analyse
relationships between different biochemical layers. Additionally, strategies are presented for variable selection in the context of omics
data and for interpreting results at the level of cellular pathways. (C)
2010 Elsevier B.V. All rights reserved.
31.
Medina, I.; Carbonell, J.; Pulido, L.; Madeira, S. C.; Goetz, S.; Conesa, A.; Tarraga, J.; Pascual-Montano, A.; Nogales-Cadenas, R.; Santoyo, J.; Garcia, F.; Marba, M.; Montaner, D.; Dopazo, J.
Babelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling Journal Article
In: NUCLEIC ACIDS RESEARCH, vol. 38, no. 2, pp. W210-W213, 2010, ISSN: 0305-1048.
@article{ISI:000284148900034,
title = {Babelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling},
author = { I. Medina and J. Carbonell and L. Pulido and S. C. Madeira and S. Goetz and A. Conesa and J. Tarraga and A. Pascual-Montano and R. Nogales-Cadenas and J. Santoyo and F. Garcia and M. Marba and D. Montaner and J. Dopazo},
url = {http://dx.doi.org/10.1093/nar/gkq388},
doi = {10.1093/nar/gkq388},
issn = {0305-1048},
year = {2010},
date = {2010-07-01},
journal = {NUCLEIC ACIDS RESEARCH},
volume = {38},
number = {2},
pages = {W210-W213},
abstract = {Babelomics is a response to the growing necessity of integrating and
analyzing different types of genomic data in an environment that allows
an easy functional interpretation of the results. Babelomics includes a
complete suite of methods for the analysis of gene expression data that
include normalization (covering most commercial platforms), pre-processing, differential gene expression (case-controls, multiclass, survival or continuous values), predictors, clustering; large-scale
genotyping assays (case controls and TDTs, and allows population
stratification analysis and correction). All these genomic data analysis
facilities are integrated and connected to multiple options for the
functional interpretation of the experiments. Different methods of
functional enrichment or gene set enrichment can be used to understand
the functional basis of the experiment analyzed. Many sources of
biological information, which include functional (GO, KEGG, Biocarta, Reactome, etc.), regulatory (Transfac, Jaspar, ORegAnno, miRNAs, etc.), text-mining or protein-protein interaction modules can be used for this
purpose. Finally a tool for the de novo functional annotation of
sequences has been included in the system. This provides support for the
functional analysis of non-model species. Mirrors of Babelomics or
command line execution of their individual components are now possible.
Babelomics is available at http://www.babelomics.org.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Babelomics is a response to the growing necessity of integrating and
analyzing different types of genomic data in an environment that allows
an easy functional interpretation of the results. Babelomics includes a
complete suite of methods for the analysis of gene expression data that
include normalization (covering most commercial platforms), pre-processing, differential gene expression (case-controls, multiclass, survival or continuous values), predictors, clustering; large-scale
genotyping assays (case controls and TDTs, and allows population
stratification analysis and correction). All these genomic data analysis
facilities are integrated and connected to multiple options for the
functional interpretation of the experiments. Different methods of
functional enrichment or gene set enrichment can be used to understand
the functional basis of the experiment analyzed. Many sources of
biological information, which include functional (GO, KEGG, Biocarta, Reactome, etc.), regulatory (Transfac, Jaspar, ORegAnno, miRNAs, etc.), text-mining or protein-protein interaction modules can be used for this
purpose. Finally a tool for the de novo functional annotation of
sequences has been included in the system. This provides support for the
functional analysis of non-model species. Mirrors of Babelomics or
command line execution of their individual components are now possible.
Babelomics is available at http://www.babelomics.org.
analyzing different types of genomic data in an environment that allows
an easy functional interpretation of the results. Babelomics includes a
complete suite of methods for the analysis of gene expression data that
include normalization (covering most commercial platforms), pre-processing, differential gene expression (case-controls, multiclass, survival or continuous values), predictors, clustering; large-scale
genotyping assays (case controls and TDTs, and allows population
stratification analysis and correction). All these genomic data analysis
facilities are integrated and connected to multiple options for the
functional interpretation of the experiments. Different methods of
functional enrichment or gene set enrichment can be used to understand
the functional basis of the experiment analyzed. Many sources of
biological information, which include functional (GO, KEGG, Biocarta, Reactome, etc.), regulatory (Transfac, Jaspar, ORegAnno, miRNAs, etc.), text-mining or protein-protein interaction modules can be used for this
purpose. Finally a tool for the de novo functional annotation of
sequences has been included in the system. This provides support for the
functional analysis of non-model species. Mirrors of Babelomics or
command line execution of their individual components are now possible.
Babelomics is available at http://www.babelomics.org.
30.
Nueda, M. Jose; Carbonell, J.; Medina, I.; Dopazo, J.; Conesa, A.
Serial Expression Analysis: a web tool for the analysis of serial gene expression data Journal Article
In: NUCLEIC ACIDS RESEARCH, vol. 38, no. 2, pp. W239-W245, 2010, ISSN: 0305-1048.
@article{ISI:000284148900039,
title = {Serial Expression Analysis: a web tool for the analysis of serial gene
expression data},
author = { M. Jose Nueda and J. Carbonell and I. Medina and J. Dopazo and A. Conesa},
url = {http://dx.doi.org/10.1093/nar/gkq488},
doi = {10.1093/nar/gkq488},
issn = {0305-1048},
year = {2010},
date = {2010-07-01},
journal = {NUCLEIC ACIDS RESEARCH},
volume = {38},
number = {2},
pages = {W239-W245},
abstract = {Serial transcriptomics experiments investigate the dynamics of gene
expression changes associated with a quantitative variable such as time
or dosage. The statistical analysis of these data implies the study of
global and gene-specific expression trends, the identification of
significant serial changes, the comparison of expression profiles and
the assessment of transcriptional changes in terms of cellular
processes. We have created the SEA (Serial Expression Analysis) suite to
provide a complete web-based resource for the analysis of serial
transcriptomics data. SEA offers five different algorithms based on
univariate, multivariate and functional profiling strategies framed
within a user-friendly interface and a project-oriented architecture to
facilitate the analysis of serial gene expression data sets from
different perspectives. SEA is available at sea.bioinfo.cipf.es.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Serial transcriptomics experiments investigate the dynamics of gene
expression changes associated with a quantitative variable such as time
or dosage. The statistical analysis of these data implies the study of
global and gene-specific expression trends, the identification of
significant serial changes, the comparison of expression profiles and
the assessment of transcriptional changes in terms of cellular
processes. We have created the SEA (Serial Expression Analysis) suite to
provide a complete web-based resource for the analysis of serial
transcriptomics data. SEA offers five different algorithms based on
univariate, multivariate and functional profiling strategies framed
within a user-friendly interface and a project-oriented architecture to
facilitate the analysis of serial gene expression data sets from
different perspectives. SEA is available at sea.bioinfo.cipf.es.
expression changes associated with a quantitative variable such as time
or dosage. The statistical analysis of these data implies the study of
global and gene-specific expression trends, the identification of
significant serial changes, the comparison of expression profiles and
the assessment of transcriptional changes in terms of cellular
processes. We have created the SEA (Serial Expression Analysis) suite to
provide a complete web-based resource for the analysis of serial
transcriptomics data. SEA offers five different algorithms based on
univariate, multivariate and functional profiling strategies framed
within a user-friendly interface and a project-oriented architecture to
facilitate the analysis of serial gene expression data sets from
different perspectives. SEA is available at sea.bioinfo.cipf.es.
29.
Nemeth, A.; Conesa, A.; Santoyo-Lopez, J.; Medina, I.; Montaner, D.; Peterfia, B.; Solovei, I.; Cremer, T.; Dopazo, J.; Laengst, G.
Initial Genomics of the Human Nucleolus Journal Article
In: PLOS GENETICS, vol. 6, no. 3, 2010, ISSN: 1553-7390.
@article{ISI:000276311400004,
title = {Initial Genomics of the Human Nucleolus},
author = { A. Nemeth and A. Conesa and J. Santoyo-Lopez and I. Medina and D. Montaner and B. Peterfia and I. Solovei and T. Cremer and J. Dopazo and G. Laengst},
url = {http://dx.doi.org/10.1371/journal.pgen.1000889},
doi = {10.1371/journal.pgen.1000889},
issn = {1553-7390},
year = {2010},
date = {2010-03-01},
journal = {PLOS GENETICS},
volume = {6},
number = {3},
abstract = {We report for the first time the genomics of a nuclear compartment of
the eukaryotic cell. 454 sequencing and microarray analysis revealed the
pattern of nucleolus-associated chromatin domains (NADs) in the linear
human genome and identified different gene families and certain
satellite repeats as the major building blocks of NADs, which constitute
about 4% of the genome. Bioinformatic evaluation showed that
NAD-localized genes take part in specific biological processes, like the
response to other organisms, odor perception, and tissue development. 3D
FISH and immunofluorescence experiments illustrated the spatial
distribution of NAD-specific chromatin within interphase nuclei and its
alteration upon transcriptional changes. Altogether, our findings
describe the nature of DNA sequences associated with the human nucleolus
and provide insights into the function of the nucleolus in genome
organization and establishment of nuclear architecture.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We report for the first time the genomics of a nuclear compartment of
the eukaryotic cell. 454 sequencing and microarray analysis revealed the
pattern of nucleolus-associated chromatin domains (NADs) in the linear
human genome and identified different gene families and certain
satellite repeats as the major building blocks of NADs, which constitute
about 4% of the genome. Bioinformatic evaluation showed that
NAD-localized genes take part in specific biological processes, like the
response to other organisms, odor perception, and tissue development. 3D
FISH and immunofluorescence experiments illustrated the spatial
distribution of NAD-specific chromatin within interphase nuclei and its
alteration upon transcriptional changes. Altogether, our findings
describe the nature of DNA sequences associated with the human nucleolus
and provide insights into the function of the nucleolus in genome
organization and establishment of nuclear architecture.
the eukaryotic cell. 454 sequencing and microarray analysis revealed the
pattern of nucleolus-associated chromatin domains (NADs) in the linear
human genome and identified different gene families and certain
satellite repeats as the major building blocks of NADs, which constitute
about 4% of the genome. Bioinformatic evaluation showed that
NAD-localized genes take part in specific biological processes, like the
response to other organisms, odor perception, and tissue development. 3D
FISH and immunofluorescence experiments illustrated the spatial
distribution of NAD-specific chromatin within interphase nuclei and its
alteration upon transcriptional changes. Altogether, our findings
describe the nature of DNA sequences associated with the human nucleolus
and provide insights into the function of the nucleolus in genome
organization and establishment of nuclear architecture.
28.
Prado-Lopez, S.; Conesa, A.; Arminan, A.; Martinez-Losa, M.; Escobedo-Lucea, C.; Gandia, C.; Tarazona, S.; Melguizo, D.; Blesa, D.; Montaner, D.; Sanz-Gonzalez, S.; Sepulveda, P.; Goetz, S.; O'Connor, J. Enrique; Moreno, R.; Dopazo, J.; Burks, D. J.; Stojkovic, M.
Hypoxia Promotes Efficient Differentiation of Human Embryonic Stem Cells to Functional Endothelium Journal Article
In: STEM CELLS, vol. 28, no. 3, pp. 407-418, 2010, ISSN: 1066-5099.
@article{ISI:000277093700004,
title = {Hypoxia Promotes Efficient Differentiation of Human Embryonic Stem Cells
to Functional Endothelium},
author = { S. Prado-Lopez and A. Conesa and A. Arminan and M. Martinez-Losa and C. Escobedo-Lucea and C. Gandia and S. Tarazona and D. Melguizo and D. Blesa and D. Montaner and S. Sanz-Gonzalez and P. Sepulveda and S. Goetz and J. Enrique O'Connor and R. Moreno and J. Dopazo and D. J. Burks and M. Stojkovic},
url = {http://dx.doi.org/10.1002/stem.295},
doi = {10.1002/stem.295},
issn = {1066-5099},
year = {2010},
date = {2010-03-01},
journal = {STEM CELLS},
volume = {28},
number = {3},
pages = {407-418},
abstract = {Early development of mammalian embryos occurs in an environment of
relative hypoxia. Nevertheless, human embryonic stem cells (hESC), which
are derived from the inner cell mass of blastocyst, are routinely
cultured under the same atmospheric conditions (21% O(2)) as somatic
cells. We hypothesized that O2 levels modulate gene expression and
differentiation potential of hESC, and thus, we performed gene profiling
of hESC maintained under normoxic or hypoxic (1% or 5% O(2))
conditions. Our analysis revealed that hypoxia downregulates expression
of pluripotency markers in hESC but increases significantly the
expression of genes associated with angio-and vasculogenesis including
vascular endothelial growth factor and angiopoitein-like proteins.
Consequently, we were able to efficiently differentiate hESC to
functional endothelial cells (EC) by varying O(2) levels; after 24 hours
at 5% O(2), more than 50% of cells were CD34+. Transplantation of
resulting endothelial-like cells improved both systolic function and
fractional shortening in a rodent model of myocardial infarction.
Moreover, analysis of the infarcted zone revealed that transplanted EC
reduced the area of fibrous scar tissue by 50%. Thus, use of hypoxic
conditions to specify the endothelial lineage suggests a novel strategy
for cellular therapies aimed at repair of damaged vasculature in
pathologies such as cerebral ischemia and myocardial infarction. STEM
CELLS 2010; 28: 407-418},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Early development of mammalian embryos occurs in an environment of
relative hypoxia. Nevertheless, human embryonic stem cells (hESC), which
are derived from the inner cell mass of blastocyst, are routinely
cultured under the same atmospheric conditions (21% O(2)) as somatic
cells. We hypothesized that O2 levels modulate gene expression and
differentiation potential of hESC, and thus, we performed gene profiling
of hESC maintained under normoxic or hypoxic (1% or 5% O(2))
conditions. Our analysis revealed that hypoxia downregulates expression
of pluripotency markers in hESC but increases significantly the
expression of genes associated with angio-and vasculogenesis including
vascular endothelial growth factor and angiopoitein-like proteins.
Consequently, we were able to efficiently differentiate hESC to
functional endothelial cells (EC) by varying O(2) levels; after 24 hours
at 5% O(2), more than 50% of cells were CD34+. Transplantation of
resulting endothelial-like cells improved both systolic function and
fractional shortening in a rodent model of myocardial infarction.
Moreover, analysis of the infarcted zone revealed that transplanted EC
reduced the area of fibrous scar tissue by 50%. Thus, use of hypoxic
conditions to specify the endothelial lineage suggests a novel strategy
for cellular therapies aimed at repair of damaged vasculature in
pathologies such as cerebral ischemia and myocardial infarction. STEM
CELLS 2010; 28: 407-418
relative hypoxia. Nevertheless, human embryonic stem cells (hESC), which
are derived from the inner cell mass of blastocyst, are routinely
cultured under the same atmospheric conditions (21% O(2)) as somatic
cells. We hypothesized that O2 levels modulate gene expression and
differentiation potential of hESC, and thus, we performed gene profiling
of hESC maintained under normoxic or hypoxic (1% or 5% O(2))
conditions. Our analysis revealed that hypoxia downregulates expression
of pluripotency markers in hESC but increases significantly the
expression of genes associated with angio-and vasculogenesis including
vascular endothelial growth factor and angiopoitein-like proteins.
Consequently, we were able to efficiently differentiate hESC to
functional endothelial cells (EC) by varying O(2) levels; after 24 hours
at 5% O(2), more than 50% of cells were CD34+. Transplantation of
resulting endothelial-like cells improved both systolic function and
fractional shortening in a rodent model of myocardial infarction.
Moreover, analysis of the infarcted zone revealed that transplanted EC
reduced the area of fibrous scar tissue by 50%. Thus, use of hypoxic
conditions to specify the endothelial lineage suggests a novel strategy
for cellular therapies aimed at repair of damaged vasculature in
pathologies such as cerebral ischemia and myocardial infarction. STEM
CELLS 2010; 28: 407-418
27.
Rattei, T.; Tischler, P.; Goetz, S.; Jehl, M.; Hoser, J.; Arnold, R.; Conesa, A.; Mewes, H.
SIMAP-a comprehensive database of pre-calculated protein sequence similarities, domains, annotations and clusters Journal Article
In: NUCLEIC ACIDS RESEARCH, vol. 38, no. 1, pp. D223-D226, 2010, ISSN: 0305-1048.
@article{ISI:000276399100033,
title = {SIMAP-a comprehensive database of pre-calculated protein sequence
similarities, domains, annotations and clusters},
author = { T. Rattei and P. Tischler and S. Goetz and M. Jehl and J. Hoser and R. Arnold and A. Conesa and H. Mewes},
url = {http://dx.doi.org/10.1093/nar/gkp949},
doi = {10.1093/nar/gkp949},
issn = {0305-1048},
year = {2010},
date = {2010-01-01},
journal = {NUCLEIC ACIDS RESEARCH},
volume = {38},
number = {1},
pages = {D223-D226},
abstract = {The prediction of protein function as well as the reconstruction of
evolutionary genesis employing sequence comparison at large is still the
most powerful tool in sequence analysis. Due to the exponential growth
of the number of known protein sequences and the subsequent quadratic
growth of the similarity matrix, the computation of the Similarity
Matrix of Proteins (SIMAP) becomes a computational intensive task. The
SIMAP database provides a comprehensive and up-to-date precalculation of
the protein sequence similarity matrix, sequence-based features and
sequence clusters. As of September 2009, SIMAP covers 48 million
proteins and more than 23 million non-redundant sequences. Novel
features of SIMAP include the expansion of the sequence space by
including databases such as ENSEMBL as well as the integration of
metagenomes based on their consistent processing and annotation.
Furthermore, protein function predictions by Blast2GO are pre-calculated
for all sequences in SIMAP and the data access and query functions have
been improved. SIMAP assists biologists to query the up-to-date sequence
space systematically and facilitates large-scale downstream projects in
computational biology. Access to SIMAP is freely provided through the
web portal for individuals (http://mips.gsf.de/simap/) and for
programmatic access through DAS (http://webclu.bio.wzw.tum.de/das/) and
Web-Service
(http://mips.gsf.de/webservices/services/SimapService2.0?wsdl).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The prediction of protein function as well as the reconstruction of
evolutionary genesis employing sequence comparison at large is still the
most powerful tool in sequence analysis. Due to the exponential growth
of the number of known protein sequences and the subsequent quadratic
growth of the similarity matrix, the computation of the Similarity
Matrix of Proteins (SIMAP) becomes a computational intensive task. The
SIMAP database provides a comprehensive and up-to-date precalculation of
the protein sequence similarity matrix, sequence-based features and
sequence clusters. As of September 2009, SIMAP covers 48 million
proteins and more than 23 million non-redundant sequences. Novel
features of SIMAP include the expansion of the sequence space by
including databases such as ENSEMBL as well as the integration of
metagenomes based on their consistent processing and annotation.
Furthermore, protein function predictions by Blast2GO are pre-calculated
for all sequences in SIMAP and the data access and query functions have
been improved. SIMAP assists biologists to query the up-to-date sequence
space systematically and facilitates large-scale downstream projects in
computational biology. Access to SIMAP is freely provided through the
web portal for individuals (http://mips.gsf.de/simap/) and for
programmatic access through DAS (http://webclu.bio.wzw.tum.de/das/) and
Web-Service
(http://mips.gsf.de/webservices/services/SimapService2.0?wsdl).
evolutionary genesis employing sequence comparison at large is still the
most powerful tool in sequence analysis. Due to the exponential growth
of the number of known protein sequences and the subsequent quadratic
growth of the similarity matrix, the computation of the Similarity
Matrix of Proteins (SIMAP) becomes a computational intensive task. The
SIMAP database provides a comprehensive and up-to-date precalculation of
the protein sequence similarity matrix, sequence-based features and
sequence clusters. As of September 2009, SIMAP covers 48 million
proteins and more than 23 million non-redundant sequences. Novel
features of SIMAP include the expansion of the sequence space by
including databases such as ENSEMBL as well as the integration of
metagenomes based on their consistent processing and annotation.
Furthermore, protein function predictions by Blast2GO are pre-calculated
for all sequences in SIMAP and the data access and query functions have
been improved. SIMAP assists biologists to query the up-to-date sequence
space systematically and facilitates large-scale downstream projects in
computational biology. Access to SIMAP is freely provided through the
web portal for individuals (http://mips.gsf.de/simap/) and for
programmatic access through DAS (http://webclu.bio.wzw.tum.de/das/) and
Web-Service
(http://mips.gsf.de/webservices/services/SimapService2.0?wsdl).
2009
26.
Brumos, J.; Colmenero-Flores, J. M.; Conesa, A.; Izquierdo, P.; Sanchez, G.; Iglesias, D. J.; Lopez-Climent, M. F.; Gomez-Cadenas, A.; Talon, M.
In: FUNCTIONAL & INTEGRATIVE GENOMICS, vol. 9, no. 3, pp. 293-309, 2009, ISSN: 1438-793X.
@article{ISI:000267339600003,
title = {Membrane transporters and carbon metabolism implicated in chloride
homeostasis differentiate salt stress responses in tolerant and
sensitive Citrus rootstocks},
author = { J. Brumos and J. M. Colmenero-Flores and A. Conesa and P. Izquierdo and G. Sanchez and D. J. Iglesias and M. F. Lopez-Climent and A. Gomez-Cadenas and M. Talon},
url = {http://dx.doi.org/10.1007/s10142-008-0107-6},
doi = {10.1007/s10142-008-0107-6},
issn = {1438-793X},
year = {2009},
date = {2009-08-01},
journal = {FUNCTIONAL & INTEGRATIVE GENOMICS},
volume = {9},
number = {3},
pages = {293-309},
abstract = {Salinity tolerance in Citrus is strongly related to leaf chloride
accumulation. Both chloride homeostasis and specific genetic responses
to Cl(-) toxicity are issues scarcely investigated in plants. To
discriminate the transcriptomic network related to Cl(-) toxicity and
salinity tolerance, we have used two Cl(-) salt treatments (NaCl and
KCl) to perform a comparative microarray approach on two Citrus
genotypes, the salt-sensitive Carrizo citrange, a poor Cl(-) excluder, and the tolerant Cleopatra mandarin, an efficient Cl(-) excluder. The
data indicated that Cl(-) toxicity, rather than Na(+) toxicity and/or
the concomitant osmotic perturbation, is the primary factor involved in
the molecular responses of citrus plant leaves to salinity. A number of
uncharacterized membrane transporter genes, like NRT1-2, were
differentially regulated in the tolerant and the sensitive genotypes, suggesting its potential implication in Cl(-) homeostasis. Analyses of
enriched functional categories showed that the tolerant rootstock
induced wider stress responses in gene expression while repressing
central metabolic processes such as photosynthesis and carbon
utilization. These features were in agreement with phenotypic changes in
the patterns of photosynthesis, transpiration, and stomatal conductance
and support the concept that regulation of transpiration and its
associated metabolic adjustments configure an adaptive response to
salinity that reduces Cl(-) accumulation in the tolerant genotype.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Salinity tolerance in Citrus is strongly related to leaf chloride
accumulation. Both chloride homeostasis and specific genetic responses
to Cl(-) toxicity are issues scarcely investigated in plants. To
discriminate the transcriptomic network related to Cl(-) toxicity and
salinity tolerance, we have used two Cl(-) salt treatments (NaCl and
KCl) to perform a comparative microarray approach on two Citrus
genotypes, the salt-sensitive Carrizo citrange, a poor Cl(-) excluder, and the tolerant Cleopatra mandarin, an efficient Cl(-) excluder. The
data indicated that Cl(-) toxicity, rather than Na(+) toxicity and/or
the concomitant osmotic perturbation, is the primary factor involved in
the molecular responses of citrus plant leaves to salinity. A number of
uncharacterized membrane transporter genes, like NRT1-2, were
differentially regulated in the tolerant and the sensitive genotypes, suggesting its potential implication in Cl(-) homeostasis. Analyses of
enriched functional categories showed that the tolerant rootstock
induced wider stress responses in gene expression while repressing
central metabolic processes such as photosynthesis and carbon
utilization. These features were in agreement with phenotypic changes in
the patterns of photosynthesis, transpiration, and stomatal conductance
and support the concept that regulation of transpiration and its
associated metabolic adjustments configure an adaptive response to
salinity that reduces Cl(-) accumulation in the tolerant genotype.
accumulation. Both chloride homeostasis and specific genetic responses
to Cl(-) toxicity are issues scarcely investigated in plants. To
discriminate the transcriptomic network related to Cl(-) toxicity and
salinity tolerance, we have used two Cl(-) salt treatments (NaCl and
KCl) to perform a comparative microarray approach on two Citrus
genotypes, the salt-sensitive Carrizo citrange, a poor Cl(-) excluder, and the tolerant Cleopatra mandarin, an efficient Cl(-) excluder. The
data indicated that Cl(-) toxicity, rather than Na(+) toxicity and/or
the concomitant osmotic perturbation, is the primary factor involved in
the molecular responses of citrus plant leaves to salinity. A number of
uncharacterized membrane transporter genes, like NRT1-2, were
differentially regulated in the tolerant and the sensitive genotypes, suggesting its potential implication in Cl(-) homeostasis. Analyses of
enriched functional categories showed that the tolerant rootstock
induced wider stress responses in gene expression while repressing
central metabolic processes such as photosynthesis and carbon
utilization. These features were in agreement with phenotypic changes in
the patterns of photosynthesis, transpiration, and stomatal conductance
and support the concept that regulation of transpiration and its
associated metabolic adjustments configure an adaptive response to
salinity that reduces Cl(-) accumulation in the tolerant genotype.
25.
Nueda, M. Jose; Sebastian, P.; Tarazona, S.; Garcia-Garcia, F.; Dopazo, J.; Ferrer, A.; Conesa, A.
Functional assessment of time course microarray data Journal Article
In: BMC BIOINFORMATICS, vol. 10, 2009, ISSN: 1471-2105, (European Molecular Biology Network Conference, Martina, ITALY, SEP 18-20, 2008).
@article{ISI:000267522200009,
title = {Functional assessment of time course microarray data},
author = { M. Jose Nueda and P. Sebastian and S. Tarazona and F. Garcia-Garcia and J. Dopazo and A. Ferrer and A. Conesa},
url = {http://dx.doi.org/10.1186/1471-2105-10-S6-S9},
doi = {10.1186/1471-2105-10-S6-S9},
issn = {1471-2105},
year = {2009},
date = {2009-01-01},
journal = {BMC BIOINFORMATICS},
volume = {10},
abstract = {Motivation: Time-course microarray experiments study the progress of
gene expression along time across one or several experimental
conditions. Most developed analysis methods focus on the clustering or
the differential expression analysis of genes and do not integrate
functional information. The assessment of the functional aspects of
time-course transcriptomics data requires the use of approaches that
exploit the activation dynamics of the functional categories to where
genes are annotated.
Methods: We present three novel methodologies for the functional
assessment of time-course microarray data. i) maSigFun derives from the
maSigPro method, a regression-based strategy to model time-dependent
expression patterns and identify genes with differences across series.
maSigFun fits a regression model for groups of genes labeled by a
functional class and selects those categories which have a significant
model. ii) PCA-maSigFun fits a PCA model of each functional
class-defined expression matrix to extract orthogonal patterns of
expression change, which are then assessed for their fit to a
time-dependent regression model. iii) ASCA-functional uses the ASCA
model to rank genes according to their correlation to principal time
expression patterns and assess functional enrichment on a GSA fashion.
We used simulated and experimental datasets to study these novel
approaches. Results were compared to alternative methodologies.
Results: Synthetic and experimental data showed that the different
methods are able to capture different aspects of the relationship
between genes, functions and co-expression that are biologically
meaningful. The methods should not be considered as competitive but they
provide different insights into the molecular and functional dynamic
events taking place within the biological system under study.},
note = {European Molecular Biology Network Conference, Martina, ITALY, SEP
18-20, 2008},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Motivation: Time-course microarray experiments study the progress of
gene expression along time across one or several experimental
conditions. Most developed analysis methods focus on the clustering or
the differential expression analysis of genes and do not integrate
functional information. The assessment of the functional aspects of
time-course transcriptomics data requires the use of approaches that
exploit the activation dynamics of the functional categories to where
genes are annotated.
Methods: We present three novel methodologies for the functional
assessment of time-course microarray data. i) maSigFun derives from the
maSigPro method, a regression-based strategy to model time-dependent
expression patterns and identify genes with differences across series.
maSigFun fits a regression model for groups of genes labeled by a
functional class and selects those categories which have a significant
model. ii) PCA-maSigFun fits a PCA model of each functional
class-defined expression matrix to extract orthogonal patterns of
expression change, which are then assessed for their fit to a
time-dependent regression model. iii) ASCA-functional uses the ASCA
model to rank genes according to their correlation to principal time
expression patterns and assess functional enrichment on a GSA fashion.
We used simulated and experimental datasets to study these novel
approaches. Results were compared to alternative methodologies.
Results: Synthetic and experimental data showed that the different
methods are able to capture different aspects of the relationship
between genes, functions and co-expression that are biologically
meaningful. The methods should not be considered as competitive but they
provide different insights into the molecular and functional dynamic
events taking place within the biological system under study.
gene expression along time across one or several experimental
conditions. Most developed analysis methods focus on the clustering or
the differential expression analysis of genes and do not integrate
functional information. The assessment of the functional aspects of
time-course transcriptomics data requires the use of approaches that
exploit the activation dynamics of the functional categories to where
genes are annotated.
Methods: We present three novel methodologies for the functional
assessment of time-course microarray data. i) maSigFun derives from the
maSigPro method, a regression-based strategy to model time-dependent
expression patterns and identify genes with differences across series.
maSigFun fits a regression model for groups of genes labeled by a
functional class and selects those categories which have a significant
model. ii) PCA-maSigFun fits a PCA model of each functional
class-defined expression matrix to extract orthogonal patterns of
expression change, which are then assessed for their fit to a
time-dependent regression model. iii) ASCA-functional uses the ASCA
model to rank genes according to their correlation to principal time
expression patterns and assess functional enrichment on a GSA fashion.
We used simulated and experimental datasets to study these novel
approaches. Results were compared to alternative methodologies.
Results: Synthetic and experimental data showed that the different
methods are able to capture different aspects of the relationship
between genes, functions and co-expression that are biologically
meaningful. The methods should not be considered as competitive but they
provide different insights into the molecular and functional dynamic
events taking place within the biological system under study.
2008
24.
Conesa, A.; Bro, R.; Garcia-Garcia, F.; Prats, J. M.; Gotz, S.; Kjeldahl, K.; Montaner, D.; Dopazo, J.
Direct functional assessment of the composite phenotype through multivariate projection strategies Journal Article
In: GENOMICS, vol. 92, no. 6, pp. 373-383, 2008, ISSN: 0888-7543.
@article{ISI:000261460100001,
title = {Direct functional assessment of the composite phenotype through
multivariate projection strategies},
author = { A. Conesa and R. Bro and F. Garcia-Garcia and J. M. Prats and S. Gotz and K. Kjeldahl and D. Montaner and J. Dopazo},
url = {http://dx.doi.org/10.1016/j.ygeno.2008.05.015},
doi = {10.1016/j.ygeno.2008.05.015},
issn = {0888-7543},
year = {2008},
date = {2008-12-01},
journal = {GENOMICS},
volume = {92},
number = {6},
pages = {373-383},
abstract = {We present a novel approach for the analysis of transcriptomics; data
that integrates functional annotation of gene sets with expression
values in a multivariate fashion, and directly assesses the relation of
functional features to a multivariate space of response phenotypical
variables. Multivariate projection methods are used to obtain new
correlated variables for a set of genes that share a given function.
These new functional variables are then related to the response
variables of interest. The analysis of the principal directions of the
multivariate regression allows for the identification of gene function
features correlated with the phenotype. Two different transcriptomics
studies are used to illustrate the statistical and interpretative
aspects of the methodology. We demonstrate the superiority of the
proposed method over equivalent approaches. (C) 2008 Elsevier Inc. All
rights reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We present a novel approach for the analysis of transcriptomics; data
that integrates functional annotation of gene sets with expression
values in a multivariate fashion, and directly assesses the relation of
functional features to a multivariate space of response phenotypical
variables. Multivariate projection methods are used to obtain new
correlated variables for a set of genes that share a given function.
These new functional variables are then related to the response
variables of interest. The analysis of the principal directions of the
multivariate regression allows for the identification of gene function
features correlated with the phenotype. Two different transcriptomics
studies are used to illustrate the statistical and interpretative
aspects of the methodology. We demonstrate the superiority of the
proposed method over equivalent approaches. (C) 2008 Elsevier Inc. All
rights reserved.
that integrates functional annotation of gene sets with expression
values in a multivariate fashion, and directly assesses the relation of
functional features to a multivariate space of response phenotypical
variables. Multivariate projection methods are used to obtain new
correlated variables for a set of genes that share a given function.
These new functional variables are then related to the response
variables of interest. The analysis of the principal directions of the
multivariate regression allows for the identification of gene function
features correlated with the phenotype. Two different transcriptomics
studies are used to illustrate the statistical and interpretative
aspects of the methodology. We demonstrate the superiority of the
proposed method over equivalent approaches. (C) 2008 Elsevier Inc. All
rights reserved.
23.
Hoogerwerf, W. A.; Sinha, M.; Conesa, A.; Luxon, B. A.; Shahinian, V. B.; Cornelissen, G.; Halberg, F.; Bostwick, J.; Timm, J.; Cassone, V. M.
Transcriptional Profiling of mRNA Expression in the Mouse Distal Colon Journal Article
In: GASTROENTEROLOGY, vol. 135, no. 6, pp. 2019-2029, 2008, ISSN: 0016-5085.
@article{ISI:000261762200064,
title = {Transcriptional Profiling of mRNA Expression in the Mouse Distal Colon},
author = { W. A. Hoogerwerf and M. Sinha and A. Conesa and B. A. Luxon and V. B. Shahinian and G. Cornelissen and F. Halberg and J. Bostwick and J. Timm and V. M. Cassone},
url = {http://dx.doi.org/10.1053/j.gastro.2008.08.048},
doi = {10.1053/j.gastro.2008.08.048},
issn = {0016-5085},
year = {2008},
date = {2008-12-01},
journal = {GASTROENTEROLOGY},
volume = {135},
number = {6},
pages = {2019-2029},
abstract = {Background & Aims: intestinal epithelial cells and the myenteric plexus
of the mouse gastrointestinal tract contain a circadian clock-based
intrinsic timekeeping system. Because disruption of the biological clock
has been associated with increased susceptibility to colon cancer and
gastrointestinal symptoms, we aimed to identify rhythmically expressed
genes in the mouse distal colon. Methods: Microarray analysis was used
to identify genes that were rhythmically expressed over a 24-hour
light/dark cycle. The transcripts were then classified according to
expression pattern, function, and association with physiologic and
pathophysiologic processes of the colon. Results: A circadian gene
expression pattern was detected in approximately 3.7% of distal.
colonic genes. A large percentage of these genes were involved in cell
signaling, differentiation, and proliferation and cell death. Of all the
rhythmically expressed genes in the mouse colon, approximately 7%
(64/906) have been associated with colorectal cancer formation (eg, B-cell leukemia/lymphoma-2 [Bcl2]) and 1.8% (18/906) with various
colonic functions such as motility and secretion (eg, vasoactive
intestinal polypeptide, cystic fibrosis transmembrane conductance
regulator). Conclusions: A subset of genes in the murine colon follows a
rhythmic expression pattern. These findings may have significant
implications for colonic physiology and pathophysiology.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background & Aims: intestinal epithelial cells and the myenteric plexus
of the mouse gastrointestinal tract contain a circadian clock-based
intrinsic timekeeping system. Because disruption of the biological clock
has been associated with increased susceptibility to colon cancer and
gastrointestinal symptoms, we aimed to identify rhythmically expressed
genes in the mouse distal colon. Methods: Microarray analysis was used
to identify genes that were rhythmically expressed over a 24-hour
light/dark cycle. The transcripts were then classified according to
expression pattern, function, and association with physiologic and
pathophysiologic processes of the colon. Results: A circadian gene
expression pattern was detected in approximately 3.7% of distal.
colonic genes. A large percentage of these genes were involved in cell
signaling, differentiation, and proliferation and cell death. Of all the
rhythmically expressed genes in the mouse colon, approximately 7%
(64/906) have been associated with colorectal cancer formation (eg, B-cell leukemia/lymphoma-2 [Bcl2]) and 1.8% (18/906) with various
colonic functions such as motility and secretion (eg, vasoactive
intestinal polypeptide, cystic fibrosis transmembrane conductance
regulator). Conclusions: A subset of genes in the murine colon follows a
rhythmic expression pattern. These findings may have significant
implications for colonic physiology and pathophysiology.
of the mouse gastrointestinal tract contain a circadian clock-based
intrinsic timekeeping system. Because disruption of the biological clock
has been associated with increased susceptibility to colon cancer and
gastrointestinal symptoms, we aimed to identify rhythmically expressed
genes in the mouse distal colon. Methods: Microarray analysis was used
to identify genes that were rhythmically expressed over a 24-hour
light/dark cycle. The transcripts were then classified according to
expression pattern, function, and association with physiologic and
pathophysiologic processes of the colon. Results: A circadian gene
expression pattern was detected in approximately 3.7% of distal.
colonic genes. A large percentage of these genes were involved in cell
signaling, differentiation, and proliferation and cell death. Of all the
rhythmically expressed genes in the mouse colon, approximately 7%
(64/906) have been associated with colorectal cancer formation (eg, B-cell leukemia/lymphoma-2 [Bcl2]) and 1.8% (18/906) with various
colonic functions such as motility and secretion (eg, vasoactive
intestinal polypeptide, cystic fibrosis transmembrane conductance
regulator). Conclusions: A subset of genes in the murine colon follows a
rhythmic expression pattern. These findings may have significant
implications for colonic physiology and pathophysiology.
22.
Stierum, R.; Conesa, A.; Heijne, W.; van Ommen, B.; Junker, K.; Scott, M. P.; Price, R. J.; Meredith, C.; Lake, B. G.; Groten, J.
In: FOOD AND CHEMICAL TOXICOLOGY, vol. 46, no. 8, pp. 2616-2628, 2008, ISSN: 0278-6915.
@article{ISI:000258440100004,
title = {Transcriptome analysis provides new insights into liver changes induced
in the rat upon dietary administration of the food additives butylated
hydroxytoluene, curcumin, propyl gallate and thiabendazole},
author = { R. Stierum and A. Conesa and W. Heijne and B. van Ommen and K. Junker and M. P. Scott and R. J. Price and C. Meredith and B. G. Lake and J. Groten},
url = {http://dx.doi.org/10.1016/j.fct.2008.04.019},
doi = {10.1016/j.fct.2008.04.019},
issn = {0278-6915},
year = {2008},
date = {2008-08-01},
journal = {FOOD AND CHEMICAL TOXICOLOGY},
volume = {46},
number = {8},
pages = {2616-2628},
abstract = {Transcriptomics was performed to gain insight into mechanisms of food
additives butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate
(PG), and thiabendazole (TB), additives for which interactions in the
liver can not be excluded. Additives were administered in diets for 28
days to Sprague-Dawley rats and cDNA microarray experiments were
performed on hepatic RNA. BHT induced changes in the expression of 10
genes, including phase I (CYP2B1/2: CYP3A9; CYP2C6) and phase II
metabolism (GST mu 2). The CYP2B1/2 and GST expression findings were
confirmed by real time RT-PCR, western blotting, and increased GST
activity towards DCNB. CC altered the expression of 12 genes. Three out
of these were related to peroxisomes (phytanoyl-CoA dioxygenase, enoyl-CoA hydratase; CYP4A3). Increased cyanide insensitive
palmitoyl-CoA oxidation was observed, suggesting that CC is a weak
peroxisome proliferator. TB changed the expression of 12 genes, including CYP1A2. In line, CYP1A2 protein expression was increased. The
expression level of five genes, associated with p53 was found to change
upon TB treatment, including p53 itself, GADD45 alpha, DN-7, protein
kinase C beta and serum albumin. These array experiments led to the
novel finding that TB is capable of inducing p53 at the protein level, at least at the highest dose levels employed above the current NOAEL.
The expression of eight genes changed upon PG administration. This study
shows the value of gene expression profiling in food toxicology in terms
of generating novel hypotheses on the mechanisms of action of food
additives in relation to pathology. (C) 2008 Elsevier Ltd. All rights
reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Transcriptomics was performed to gain insight into mechanisms of food
additives butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate
(PG), and thiabendazole (TB), additives for which interactions in the
liver can not be excluded. Additives were administered in diets for 28
days to Sprague-Dawley rats and cDNA microarray experiments were
performed on hepatic RNA. BHT induced changes in the expression of 10
genes, including phase I (CYP2B1/2: CYP3A9; CYP2C6) and phase II
metabolism (GST mu 2). The CYP2B1/2 and GST expression findings were
confirmed by real time RT-PCR, western blotting, and increased GST
activity towards DCNB. CC altered the expression of 12 genes. Three out
of these were related to peroxisomes (phytanoyl-CoA dioxygenase, enoyl-CoA hydratase; CYP4A3). Increased cyanide insensitive
palmitoyl-CoA oxidation was observed, suggesting that CC is a weak
peroxisome proliferator. TB changed the expression of 12 genes, including CYP1A2. In line, CYP1A2 protein expression was increased. The
expression level of five genes, associated with p53 was found to change
upon TB treatment, including p53 itself, GADD45 alpha, DN-7, protein
kinase C beta and serum albumin. These array experiments led to the
novel finding that TB is capable of inducing p53 at the protein level, at least at the highest dose levels employed above the current NOAEL.
The expression of eight genes changed upon PG administration. This study
shows the value of gene expression profiling in food toxicology in terms
of generating novel hypotheses on the mechanisms of action of food
additives in relation to pathology. (C) 2008 Elsevier Ltd. All rights
reserved.
additives butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate
(PG), and thiabendazole (TB), additives for which interactions in the
liver can not be excluded. Additives were administered in diets for 28
days to Sprague-Dawley rats and cDNA microarray experiments were
performed on hepatic RNA. BHT induced changes in the expression of 10
genes, including phase I (CYP2B1/2: CYP3A9; CYP2C6) and phase II
metabolism (GST mu 2). The CYP2B1/2 and GST expression findings were
confirmed by real time RT-PCR, western blotting, and increased GST
activity towards DCNB. CC altered the expression of 12 genes. Three out
of these were related to peroxisomes (phytanoyl-CoA dioxygenase, enoyl-CoA hydratase; CYP4A3). Increased cyanide insensitive
palmitoyl-CoA oxidation was observed, suggesting that CC is a weak
peroxisome proliferator. TB changed the expression of 12 genes, including CYP1A2. In line, CYP1A2 protein expression was increased. The
expression level of five genes, associated with p53 was found to change
upon TB treatment, including p53 itself, GADD45 alpha, DN-7, protein
kinase C beta and serum albumin. These array experiments led to the
novel finding that TB is capable of inducing p53 at the protein level, at least at the highest dose levels employed above the current NOAEL.
The expression of eight genes changed upon PG administration. This study
shows the value of gene expression profiling in food toxicology in terms
of generating novel hypotheses on the mechanisms of action of food
additives in relation to pathology. (C) 2008 Elsevier Ltd. All rights
reserved.
21.
Tarraga, J.; Medina, I.; Carbonell, J.; Huerta-Cepas, J.; Minguez, P.; Alloza, E.; Al-Shahrour, F.; Vegas-Azcarate, S.; Goetz, S.; Escobar, P.; Garcia-Garcia, F.; Conesa, A.; Montaner, D.; Dopazo, J.
GEPAS, a web-based tool for microarray data analysis and interpretation Journal Article
In: NUCLEIC ACIDS RESEARCH, vol. 36, no. S, pp. W308-W314, 2008, ISSN: 0305-1048.
@article{ISI:000258142300058,
title = {GEPAS, a web-based tool for microarray data analysis and interpretation},
author = { J. Tarraga and I. Medina and J. Carbonell and J. Huerta-Cepas and P. Minguez and E. Alloza and F. Al-Shahrour and S. Vegas-Azcarate and S. Goetz and P. Escobar and F. Garcia-Garcia and A. Conesa and D. Montaner and J. Dopazo},
url = {http://dx.doi.org/10.1093/nar/gkn303},
doi = {10.1093/nar/gkn303},
issn = {0305-1048},
year = {2008},
date = {2008-07-01},
journal = {NUCLEIC ACIDS RESEARCH},
volume = {36},
number = {S},
pages = {W308-W314},
abstract = {Gene Expression Profile Analysis Suite (GEPAS) is one of the most
complete and extensively used web-based packages for microarray data
analysis. During its more than 5 years of activity it has continuously
been updated to keep pace with the state-of-the-art in the changing
microarray data analysis arena. GEPAS offers diverse analysis options
that include well established as well as novel algorithms for
normalization, gene selection, class prediction, clustering and
functional profiling of the experiment. New options for time-course (or
dose-response) experiments, microarray-based class prediction, new
clustering methods and new tests for differential expression have been
included. The new pipeliner module allows automating the execution of
sequential analysis steps by means of a simple but powerful graphic
interface. An extensive re-engineering of GEPAS has been carried out
which includes the use of web services and Web 2.0 technology features, a new user interface with persistent sessions and a new extended
database of gene identifiers. GEPAS is nowadays the most quoted web tool
in its field and it is extensively used by researchers of many countries
and its records indicate an average usage rate of 500 experiments per
day. GEPAS, is available at http://www.gepas.org.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gene Expression Profile Analysis Suite (GEPAS) is one of the most
complete and extensively used web-based packages for microarray data
analysis. During its more than 5 years of activity it has continuously
been updated to keep pace with the state-of-the-art in the changing
microarray data analysis arena. GEPAS offers diverse analysis options
that include well established as well as novel algorithms for
normalization, gene selection, class prediction, clustering and
functional profiling of the experiment. New options for time-course (or
dose-response) experiments, microarray-based class prediction, new
clustering methods and new tests for differential expression have been
included. The new pipeliner module allows automating the execution of
sequential analysis steps by means of a simple but powerful graphic
interface. An extensive re-engineering of GEPAS has been carried out
which includes the use of web services and Web 2.0 technology features, a new user interface with persistent sessions and a new extended
database of gene identifiers. GEPAS is nowadays the most quoted web tool
in its field and it is extensively used by researchers of many countries
and its records indicate an average usage rate of 500 experiments per
day. GEPAS, is available at http://www.gepas.org.
complete and extensively used web-based packages for microarray data
analysis. During its more than 5 years of activity it has continuously
been updated to keep pace with the state-of-the-art in the changing
microarray data analysis arena. GEPAS offers diverse analysis options
that include well established as well as novel algorithms for
normalization, gene selection, class prediction, clustering and
functional profiling of the experiment. New options for time-course (or
dose-response) experiments, microarray-based class prediction, new
clustering methods and new tests for differential expression have been
included. The new pipeliner module allows automating the execution of
sequential analysis steps by means of a simple but powerful graphic
interface. An extensive re-engineering of GEPAS has been carried out
which includes the use of web services and Web 2.0 technology features, a new user interface with persistent sessions and a new extended
database of gene identifiers. GEPAS is nowadays the most quoted web tool
in its field and it is extensively used by researchers of many countries
and its records indicate an average usage rate of 500 experiments per
day. GEPAS, is available at http://www.gepas.org.
20.
Al-Shahrour, F.; Carbonell, J.; Minguez, P.; Goetz, S.; Conesa, A.; Tarrraga, J.; Medina, I.; Alloza, E.; Montaner, D.; Dopazo, J.
Babelomics: advanced functional profiling of transcriptomics, proteomics and genomics experiments Journal Article
In: NUCLEIC ACIDS RESEARCH, vol. 36, no. S, pp. W341-W346, 2008, ISSN: 0305-1048.
@article{ISI:000258142300064,
title = {Babelomics: advanced functional profiling of transcriptomics, proteomics
and genomics experiments},
author = { F. Al-Shahrour and J. Carbonell and P. Minguez and S. Goetz and A. Conesa and J. Tarrraga and I. Medina and E. Alloza and D. Montaner and J. Dopazo},
url = {http://dx.doi.org/10.1093/nar/gkn318},
doi = {10.1093/nar/gkn318},
issn = {0305-1048},
year = {2008},
date = {2008-07-01},
journal = {NUCLEIC ACIDS RESEARCH},
volume = {36},
number = {S},
pages = {W341-W346},
abstract = {We present a new version of Babelomics, a complete suite of web tools
for the functional profiling of genome scale experiments, with new and
improved methods as well as more types of functional definitions.
Babelomics includes different flavours of conventional functional
enrichment methods as well as more advanced gene set analysis methods
that makes it a unique tool among the similar resources available. In
addition to the well-known functional definitions (GO, KEGG), Babelomics
includes new ones such as Biocarta pathways or text mining-derived
functional terms. Regulatory modules implemented include transcriptional
control (Transfac, CisRed) and other levels of regulation such as
miRNA-mediated interference. Moreover, Babelomics allows for
sub-selection of terms in order to test more focused hypothesis. Also
gene annotation correspondence tables can be imported, which allows
testing with user-defined functional modules. Finally, a tool for the de
novo functional annotation of sequences has been included in the system.
This allows using yet unannotated organisms in the program. Babelomics
has been extensively re-engineered and now it includes the use of web
services and Web 2.0 technology features, a new user interface with
persistent sessions and a new extended database of gene identifiers.
Babelomics is available at http://www.babelomics.org.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We present a new version of Babelomics, a complete suite of web tools
for the functional profiling of genome scale experiments, with new and
improved methods as well as more types of functional definitions.
Babelomics includes different flavours of conventional functional
enrichment methods as well as more advanced gene set analysis methods
that makes it a unique tool among the similar resources available. In
addition to the well-known functional definitions (GO, KEGG), Babelomics
includes new ones such as Biocarta pathways or text mining-derived
functional terms. Regulatory modules implemented include transcriptional
control (Transfac, CisRed) and other levels of regulation such as
miRNA-mediated interference. Moreover, Babelomics allows for
sub-selection of terms in order to test more focused hypothesis. Also
gene annotation correspondence tables can be imported, which allows
testing with user-defined functional modules. Finally, a tool for the de
novo functional annotation of sequences has been included in the system.
This allows using yet unannotated organisms in the program. Babelomics
has been extensively re-engineered and now it includes the use of web
services and Web 2.0 technology features, a new user interface with
persistent sessions and a new extended database of gene identifiers.
Babelomics is available at http://www.babelomics.org.
for the functional profiling of genome scale experiments, with new and
improved methods as well as more types of functional definitions.
Babelomics includes different flavours of conventional functional
enrichment methods as well as more advanced gene set analysis methods
that makes it a unique tool among the similar resources available. In
addition to the well-known functional definitions (GO, KEGG), Babelomics
includes new ones such as Biocarta pathways or text mining-derived
functional terms. Regulatory modules implemented include transcriptional
control (Transfac, CisRed) and other levels of regulation such as
miRNA-mediated interference. Moreover, Babelomics allows for
sub-selection of terms in order to test more focused hypothesis. Also
gene annotation correspondence tables can be imported, which allows
testing with user-defined functional modules. Finally, a tool for the de
novo functional annotation of sequences has been included in the system.
This allows using yet unannotated organisms in the program. Babelomics
has been extensively re-engineered and now it includes the use of web
services and Web 2.0 technology features, a new user interface with
persistent sessions and a new extended database of gene identifiers.
Babelomics is available at http://www.babelomics.org.
19.
Botton, A.; Galla, G.; Conesa, A.; Bachem, C.; Ramina, A.; Barcaccia, G.
Large-scale Gene Ontology analysis of plant transcriptome-derived sequences retrieved by AFLP technology Journal Article
In: BMC GENOMICS, vol. 9, 2008, ISSN: 1471-2164.
@article{ISI:000258552300001,
title = {Large-scale Gene Ontology analysis of plant transcriptome-derived
sequences retrieved by AFLP technology},
author = { A. Botton and G. Galla and A. Conesa and C. Bachem and A. Ramina and G. Barcaccia},
url = {http://dx.doi.org/10.1186/1471-2164-9-347},
doi = {10.1186/1471-2164-9-347},
issn = {1471-2164},
year = {2008},
date = {2008-07-01},
journal = {BMC GENOMICS},
volume = {9},
abstract = {Background: After 10-year-use of AFLP (Amplified Fragment Length
Polymorphism) technology for DNA fingerprinting and mRNA profiling, large repertories of genome- and transcriptome-derived sequences are
available in public databases for model, crop and tree species. AFLP
marker systems have been and are being extensively exploited for genome
scanning and gene mapping, as well as cDNA-AFLP for transcriptome
profiling and differentially expressed gene cloning. The evaluation, annotation and classification of genomic markers and expressed
transcripts would be of great utility for both functional genomics and
systems biology research in plants. This may be achieved by means of the
Gene Ontology (GO), consisting in three structured vocabularies (i.e.
ontologies) describing genes, transcripts and proteins of any organism
in terms of their associated cellular component, biological process and
molecular function in a species-independent manner. In this paper, the
functional annotation of about 8,000 AFLP-derived ESTs retrieved in the
NCBI databases was carried out by using GO terminology.
Results: Descriptive statistics on the type, size and nature of gene
sequences obtained by means of AFLP technology were calculated. The gene
products associated with mRNA transcripts were then classified according
to the three main GO vocabularies. A comparison of the functional
content of cDNA-AFLP records was also performed by splitting the
sequence dataset into monocots and dicots and by comparing them to all
annotated ESTs of Arabidopsis and rice, respectively. On the whole, the
statistical parameters adopted for the in silico AFLP-derived
transcriptome-anchored sequence analysis proved to be critical for
obtaining reliable GO results. Such an exhaustive annotation may offer a
suitable platform for functional genomics, particularly useful in
non-model species.
Conclusion: Reliable GO annotations of AFLP-derived sequences can be
gathered through the optimization of the experimental steps and the
statistical parameters adopted. The Blast2GO software was shown to
represent a comprehensive bioinformatics solution for an
annotation-based functional analysis. According to the whole set of GO
annotations, the AFLP technology generates thorough information for
angiosperm gene products and shares common features across angiosperm
species and families. The utility of this technology for structural and
functional genomics in plants can be implemented by serial annotation
analyses of genome- anchored fragments and organ/tissue-specific
repertories of transcriptome-derived fragments.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: After 10-year-use of AFLP (Amplified Fragment Length
Polymorphism) technology for DNA fingerprinting and mRNA profiling, large repertories of genome- and transcriptome-derived sequences are
available in public databases for model, crop and tree species. AFLP
marker systems have been and are being extensively exploited for genome
scanning and gene mapping, as well as cDNA-AFLP for transcriptome
profiling and differentially expressed gene cloning. The evaluation, annotation and classification of genomic markers and expressed
transcripts would be of great utility for both functional genomics and
systems biology research in plants. This may be achieved by means of the
Gene Ontology (GO), consisting in three structured vocabularies (i.e.
ontologies) describing genes, transcripts and proteins of any organism
in terms of their associated cellular component, biological process and
molecular function in a species-independent manner. In this paper, the
functional annotation of about 8,000 AFLP-derived ESTs retrieved in the
NCBI databases was carried out by using GO terminology.
Results: Descriptive statistics on the type, size and nature of gene
sequences obtained by means of AFLP technology were calculated. The gene
products associated with mRNA transcripts were then classified according
to the three main GO vocabularies. A comparison of the functional
content of cDNA-AFLP records was also performed by splitting the
sequence dataset into monocots and dicots and by comparing them to all
annotated ESTs of Arabidopsis and rice, respectively. On the whole, the
statistical parameters adopted for the in silico AFLP-derived
transcriptome-anchored sequence analysis proved to be critical for
obtaining reliable GO results. Such an exhaustive annotation may offer a
suitable platform for functional genomics, particularly useful in
non-model species.
Conclusion: Reliable GO annotations of AFLP-derived sequences can be
gathered through the optimization of the experimental steps and the
statistical parameters adopted. The Blast2GO software was shown to
represent a comprehensive bioinformatics solution for an
annotation-based functional analysis. According to the whole set of GO
annotations, the AFLP technology generates thorough information for
angiosperm gene products and shares common features across angiosperm
species and families. The utility of this technology for structural and
functional genomics in plants can be implemented by serial annotation
analyses of genome- anchored fragments and organ/tissue-specific
repertories of transcriptome-derived fragments.
Polymorphism) technology for DNA fingerprinting and mRNA profiling, large repertories of genome- and transcriptome-derived sequences are
available in public databases for model, crop and tree species. AFLP
marker systems have been and are being extensively exploited for genome
scanning and gene mapping, as well as cDNA-AFLP for transcriptome
profiling and differentially expressed gene cloning. The evaluation, annotation and classification of genomic markers and expressed
transcripts would be of great utility for both functional genomics and
systems biology research in plants. This may be achieved by means of the
Gene Ontology (GO), consisting in three structured vocabularies (i.e.
ontologies) describing genes, transcripts and proteins of any organism
in terms of their associated cellular component, biological process and
molecular function in a species-independent manner. In this paper, the
functional annotation of about 8,000 AFLP-derived ESTs retrieved in the
NCBI databases was carried out by using GO terminology.
Results: Descriptive statistics on the type, size and nature of gene
sequences obtained by means of AFLP technology were calculated. The gene
products associated with mRNA transcripts were then classified according
to the three main GO vocabularies. A comparison of the functional
content of cDNA-AFLP records was also performed by splitting the
sequence dataset into monocots and dicots and by comparing them to all
annotated ESTs of Arabidopsis and rice, respectively. On the whole, the
statistical parameters adopted for the in silico AFLP-derived
transcriptome-anchored sequence analysis proved to be critical for
obtaining reliable GO results. Such an exhaustive annotation may offer a
suitable platform for functional genomics, particularly useful in
non-model species.
Conclusion: Reliable GO annotations of AFLP-derived sequences can be
gathered through the optimization of the experimental steps and the
statistical parameters adopted. The Blast2GO software was shown to
represent a comprehensive bioinformatics solution for an
annotation-based functional analysis. According to the whole set of GO
annotations, the AFLP technology generates thorough information for
angiosperm gene products and shares common features across angiosperm
species and families. The utility of this technology for structural and
functional genomics in plants can be implemented by serial annotation
analyses of genome- anchored fragments and organ/tissue-specific
repertories of transcriptome-derived fragments.
18.
Gotz, S.; Garcia-Gomez, J. M.; Terol, J.; Williams, T. D.; Nagaraj, S. H.; Nueda, M. J.; Robles, M.; Talon, M.; Dopazo, J.; Conesa, A.
High-throughput functional annotation and data mining with the Blast2GO suite Journal Article
In: NUCLEIC ACIDS RESEARCH, vol. 36, no. 10, pp. 3420-3435, 2008, ISSN: 0305-1048.
@article{ISI:000257183200025,
title = {High-throughput functional annotation and data mining with the Blast2GO
suite},
author = { S. Gotz and J. M. Garcia-Gomez and J. Terol and T. D. Williams and S. H. Nagaraj and M. J. Nueda and M. Robles and M. Talon and J. Dopazo and A. Conesa},
url = {http://dx.doi.org/10.1093/nar/gkn176},
doi = {10.1093/nar/gkn176},
issn = {0305-1048},
year = {2008},
date = {2008-06-01},
journal = {NUCLEIC ACIDS RESEARCH},
volume = {36},
number = {10},
pages = {3420-3435},
abstract = {Functional genomics technologies have been widely adopted in the
biological research of both model and non-model species. An efficient
functional annotation of DNA or protein sequences is a major requirement
for the successful application of these approaches as functional
information on gene products is often the key to the interpretation of
experimental results. Therefore, there is an increasing need for
bioinformatics resources which are able to cope with large amount of
sequence data, produce valuable annotation results and are easily
accessible to laboratories where functional genomics projects are being
undertaken. We present the Blast2GO suite as an integrated and
biologist-oriented solution for the high-throughput and automatic
functional annotation of DNA or protein sequences based on the Gene
Ontology vocabulary. The most outstanding Blast2GO features are: (i) the
combination of various annotation strategies and tools controlling type
and intensity of annotation, (ii) the numerous graphical features such
as the interactive GO-graph visualization for gene-set function
profiling or descriptive charts, (iii) the general sequence management
features and (iv) high-throughput capabilities. We used the Blast2GO
framework to carry out a detailed analysis of annotation behaviour
through homology transfer and its impact in functional genomics
research. Our aim is to offer biologists useful information to take into
account when addressing the task of functionally characterizing their
sequence data.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Functional genomics technologies have been widely adopted in the
biological research of both model and non-model species. An efficient
functional annotation of DNA or protein sequences is a major requirement
for the successful application of these approaches as functional
information on gene products is often the key to the interpretation of
experimental results. Therefore, there is an increasing need for
bioinformatics resources which are able to cope with large amount of
sequence data, produce valuable annotation results and are easily
accessible to laboratories where functional genomics projects are being
undertaken. We present the Blast2GO suite as an integrated and
biologist-oriented solution for the high-throughput and automatic
functional annotation of DNA or protein sequences based on the Gene
Ontology vocabulary. The most outstanding Blast2GO features are: (i) the
combination of various annotation strategies and tools controlling type
and intensity of annotation, (ii) the numerous graphical features such
as the interactive GO-graph visualization for gene-set function
profiling or descriptive charts, (iii) the general sequence management
features and (iv) high-throughput capabilities. We used the Blast2GO
framework to carry out a detailed analysis of annotation behaviour
through homology transfer and its impact in functional genomics
research. Our aim is to offer biologists useful information to take into
account when addressing the task of functionally characterizing their
sequence data.
biological research of both model and non-model species. An efficient
functional annotation of DNA or protein sequences is a major requirement
for the successful application of these approaches as functional
information on gene products is often the key to the interpretation of
experimental results. Therefore, there is an increasing need for
bioinformatics resources which are able to cope with large amount of
sequence data, produce valuable annotation results and are easily
accessible to laboratories where functional genomics projects are being
undertaken. We present the Blast2GO suite as an integrated and
biologist-oriented solution for the high-throughput and automatic
functional annotation of DNA or protein sequences based on the Gene
Ontology vocabulary. The most outstanding Blast2GO features are: (i) the
combination of various annotation strategies and tools controlling type
and intensity of annotation, (ii) the numerous graphical features such
as the interactive GO-graph visualization for gene-set function
profiling or descriptive charts, (iii) the general sequence management
features and (iv) high-throughput capabilities. We used the Blast2GO
framework to carry out a detailed analysis of annotation behaviour
through homology transfer and its impact in functional genomics
research. Our aim is to offer biologists useful information to take into
account when addressing the task of functionally characterizing their
sequence data.
17.
Agudo, M.; Perez-Marin, M. C.; Loenngren, U.; Sobrado, P.; Conesa, A.; Canovas, I.; Salinas-Navarro, M.; Miralles-Imperial, J.; Hallbook, F.; Vidal-Sanz, M.
Time course profiling of the retinal transcriptome after optic nerve transection and optic nerve crush Journal Article
In: MOLECULAR VISION, vol. 14, no. 126, pp. 1050-1063, 2008, ISSN: 1090-0535.
@article{ISI:000257750100001,
title = {Time course profiling of the retinal transcriptome after optic nerve
transection and optic nerve crush},
author = { M. Agudo and M. C. Perez-Marin and U. Loenngren and P. Sobrado and A. Conesa and I. Canovas and M. Salinas-Navarro and J. Miralles-Imperial and F. Hallbook and M. Vidal-Sanz},
issn = {1090-0535},
year = {2008},
date = {2008-06-01},
journal = {MOLECULAR VISION},
volume = {14},
number = {126},
pages = {1050-1063},
abstract = {Purpose: A time-course analysis of gene regulation in the adult rat
retina after intraorbital nerve crush (IONC) and intraorbital nerve
transection (IONT).
Methods: RNA was extracted from adult rat retinas undergoing either IONT
or IONC at increasing times post-lesion. Affymetrix RAE230.2 arrays were
hybridized and analyzed. Statistically regulated genes were annotated
and functionally clustered. Arrays were validated by means of quantative
reverse transcription polymerase chain reaction (qRT-PCR) on ten
regulated genes at two times post-lesion. Western blotting and
immunohistofluorescence for four pro-apoptotic proteins were performed
on naive and injured retinas. Finally, custom signaling maps for IONT-
and IONC-induced death response were generated (MetaCore, Genego Inc.).
Results: Here we show that over time, 3,219 sequences were regulated
after IONT and 1,996 after IONC. Out of the total of regulated
sequences, 1,078 were commonly regulated by both injuries.
Interestingly, while IONT mainly triggers a gene upregulation-sustained
over time, IONC causes a transitory downregulation. Functional
clustering identified the regulation of high interest biologic
processes, most importantly cell death wherein apoptosis was the most
significant cluster. Ten death-related genes upregulated by both
injuries were used for array validation by means of qRT-PCR. In
addition, western blotting and immunohistofluorescence of total and
active Caspase 3 (Casp3), tumor necrosis factor receptor type 1
associated death domain (TRADD), tumor necrosis factor receptor
superfamily member 1a (TNFR1a), and c-fos were performed to confirm
their protein regulation and expression pattern in nave and injured
retinas. These analyses demonstrated that for these genes, protein
regulation followed transcriptional regulation and that these
proapoptotic proteins were expressed by retinal ganglion cells (RGCs).
MetaCore-based death-signaling maps show that several apoptotic cascades
were regulated in the retina following optic nerve injury and highlight
the similarities and differences between IONT and IONC in cell death
profiling.
Conclusions: This comprehensive time course retinal transcriptome study
comparing IONT and IONC lesions provides a unique valuable tool to
understand the molecular mechanisms underlying optic nerve injury and to
design neuroprotective protocols.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Purpose: A time-course analysis of gene regulation in the adult rat
retina after intraorbital nerve crush (IONC) and intraorbital nerve
transection (IONT).
Methods: RNA was extracted from adult rat retinas undergoing either IONT
or IONC at increasing times post-lesion. Affymetrix RAE230.2 arrays were
hybridized and analyzed. Statistically regulated genes were annotated
and functionally clustered. Arrays were validated by means of quantative
reverse transcription polymerase chain reaction (qRT-PCR) on ten
regulated genes at two times post-lesion. Western blotting and
immunohistofluorescence for four pro-apoptotic proteins were performed
on naive and injured retinas. Finally, custom signaling maps for IONT-
and IONC-induced death response were generated (MetaCore, Genego Inc.).
Results: Here we show that over time, 3,219 sequences were regulated
after IONT and 1,996 after IONC. Out of the total of regulated
sequences, 1,078 were commonly regulated by both injuries.
Interestingly, while IONT mainly triggers a gene upregulation-sustained
over time, IONC causes a transitory downregulation. Functional
clustering identified the regulation of high interest biologic
processes, most importantly cell death wherein apoptosis was the most
significant cluster. Ten death-related genes upregulated by both
injuries were used for array validation by means of qRT-PCR. In
addition, western blotting and immunohistofluorescence of total and
active Caspase 3 (Casp3), tumor necrosis factor receptor type 1
associated death domain (TRADD), tumor necrosis factor receptor
superfamily member 1a (TNFR1a), and c-fos were performed to confirm
their protein regulation and expression pattern in nave and injured
retinas. These analyses demonstrated that for these genes, protein
regulation followed transcriptional regulation and that these
proapoptotic proteins were expressed by retinal ganglion cells (RGCs).
MetaCore-based death-signaling maps show that several apoptotic cascades
were regulated in the retina following optic nerve injury and highlight
the similarities and differences between IONT and IONC in cell death
profiling.
Conclusions: This comprehensive time course retinal transcriptome study
comparing IONT and IONC lesions provides a unique valuable tool to
understand the molecular mechanisms underlying optic nerve injury and to
design neuroprotective protocols.
retina after intraorbital nerve crush (IONC) and intraorbital nerve
transection (IONT).
Methods: RNA was extracted from adult rat retinas undergoing either IONT
or IONC at increasing times post-lesion. Affymetrix RAE230.2 arrays were
hybridized and analyzed. Statistically regulated genes were annotated
and functionally clustered. Arrays were validated by means of quantative
reverse transcription polymerase chain reaction (qRT-PCR) on ten
regulated genes at two times post-lesion. Western blotting and
immunohistofluorescence for four pro-apoptotic proteins were performed
on naive and injured retinas. Finally, custom signaling maps for IONT-
and IONC-induced death response were generated (MetaCore, Genego Inc.).
Results: Here we show that over time, 3,219 sequences were regulated
after IONT and 1,996 after IONC. Out of the total of regulated
sequences, 1,078 were commonly regulated by both injuries.
Interestingly, while IONT mainly triggers a gene upregulation-sustained
over time, IONC causes a transitory downregulation. Functional
clustering identified the regulation of high interest biologic
processes, most importantly cell death wherein apoptosis was the most
significant cluster. Ten death-related genes upregulated by both
injuries were used for array validation by means of qRT-PCR. In
addition, western blotting and immunohistofluorescence of total and
active Caspase 3 (Casp3), tumor necrosis factor receptor type 1
associated death domain (TRADD), tumor necrosis factor receptor
superfamily member 1a (TNFR1a), and c-fos were performed to confirm
their protein regulation and expression pattern in nave and injured
retinas. These analyses demonstrated that for these genes, protein
regulation followed transcriptional regulation and that these
proapoptotic proteins were expressed by retinal ganglion cells (RGCs).
MetaCore-based death-signaling maps show that several apoptotic cascades
were regulated in the retina following optic nerve injury and highlight
the similarities and differences between IONT and IONC in cell death
profiling.
Conclusions: This comprehensive time course retinal transcriptome study
comparing IONT and IONC lesions provides a unique valuable tool to
understand the molecular mechanisms underlying optic nerve injury and to
design neuroprotective protocols.
2007
16.
Levin, A. M.; de Vries, R. P.; Conesa, A.; de Bekker, C.; Talon, M.; Menke, H. H.; van Peij, N. N. M. E.; Wosten, H. A. B.
Spatial differentiation in the vegetative mycelium of Aspergillus niger Journal Article
In: EUKARYOTIC CELL, vol. 6, no. 12, pp. 2311-2322, 2007, ISSN: 1535-9778.
@article{ISI:000251896100016,
title = {Spatial differentiation in the vegetative mycelium of Aspergillus niger},
author = { A. M. Levin and R. P. de Vries and A. Conesa and C. de Bekker and M. Talon and H. H. Menke and N. N. M. E. van Peij and H. A. B. Wosten},
url = {http://dx.doi.org/10.1128/EC.00244-07},
doi = {10.1128/EC.00244-07},
issn = {1535-9778},
year = {2007},
date = {2007-12-01},
journal = {EUKARYOTIC CELL},
volume = {6},
number = {12},
pages = {2311-2322},
abstract = {Fungal mycelia are exposed to heterogenic substrates. The substrate in
the central part of the colony has been (partly) degraded, whereas it is
still unexplored at the periphery of the mycelium. We here assessed
whether substrate heterogeneity is a main determinant of spatial gene
expression in colonies of Aspergillus niger. This question was addressed
by analyzing whole-genome gene expression in five concentric zones of
7-day-old maltose- and xylose-grown colonies. Expression profiles at the
periphery and the center were clearly different. More than 25% of the
active genes showed twofold differences in expression between the inner
and outermost zones of the colony. Moreover, 9% of the genes were
expressed in only one of the five concentric zones, showing that a
considerable part of the genome is active in a restricted part of the
colony only. Statistical analysis of expression profiles of colonies
that had either been or not been transferred to fresh xylose-containing
medium showed that differential expression in a colony is due to the
heterogeneity of the medium (e.g., genes involved in secretion, genes
encoding proteases, and genes involved in xylose metabolism) as well as
to medium-independent mechanisms (e.g., genes involved in nitrate
metabolism and genes involved in cell wall synthesis and modification).
Thus, we conclude that the mycelia of 7-day-old colonies of A. niger are
highly differentiated. This conclusion is also indicated by the fact
that distinct zones of the colony grow and secrete proteins, even after
transfer to fresh medium.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Fungal mycelia are exposed to heterogenic substrates. The substrate in
the central part of the colony has been (partly) degraded, whereas it is
still unexplored at the periphery of the mycelium. We here assessed
whether substrate heterogeneity is a main determinant of spatial gene
expression in colonies of Aspergillus niger. This question was addressed
by analyzing whole-genome gene expression in five concentric zones of
7-day-old maltose- and xylose-grown colonies. Expression profiles at the
periphery and the center were clearly different. More than 25% of the
active genes showed twofold differences in expression between the inner
and outermost zones of the colony. Moreover, 9% of the genes were
expressed in only one of the five concentric zones, showing that a
considerable part of the genome is active in a restricted part of the
colony only. Statistical analysis of expression profiles of colonies
that had either been or not been transferred to fresh xylose-containing
medium showed that differential expression in a colony is due to the
heterogeneity of the medium (e.g., genes involved in secretion, genes
encoding proteases, and genes involved in xylose metabolism) as well as
to medium-independent mechanisms (e.g., genes involved in nitrate
metabolism and genes involved in cell wall synthesis and modification).
Thus, we conclude that the mycelia of 7-day-old colonies of A. niger are
highly differentiated. This conclusion is also indicated by the fact
that distinct zones of the colony grow and secrete proteins, even after
transfer to fresh medium.
the central part of the colony has been (partly) degraded, whereas it is
still unexplored at the periphery of the mycelium. We here assessed
whether substrate heterogeneity is a main determinant of spatial gene
expression in colonies of Aspergillus niger. This question was addressed
by analyzing whole-genome gene expression in five concentric zones of
7-day-old maltose- and xylose-grown colonies. Expression profiles at the
periphery and the center were clearly different. More than 25% of the
active genes showed twofold differences in expression between the inner
and outermost zones of the colony. Moreover, 9% of the genes were
expressed in only one of the five concentric zones, showing that a
considerable part of the genome is active in a restricted part of the
colony only. Statistical analysis of expression profiles of colonies
that had either been or not been transferred to fresh xylose-containing
medium showed that differential expression in a colony is due to the
heterogeneity of the medium (e.g., genes involved in secretion, genes
encoding proteases, and genes involved in xylose metabolism) as well as
to medium-independent mechanisms (e.g., genes involved in nitrate
metabolism and genes involved in cell wall synthesis and modification).
Thus, we conclude that the mycelia of 7-day-old colonies of A. niger are
highly differentiated. This conclusion is also indicated by the fact
that distinct zones of the colony grow and secrete proteins, even after
transfer to fresh medium.
15.
Gandia, M.; Conesa, A.; Ancillo, G.; Gadea, J.; Forment, J.; Pallas, V.; Flores, R.; Duran-Vila, N.; Moreno, P.; Guerri, J.
Transcriptional response of Citrus aurantifolia to infection by Citrus tristeza virus Journal Article
In: VIROLOGY, vol. 367, no. 2, pp. 298-306, 2007, ISSN: 0042-6822.
@article{ISI:000250162900007,
title = {Transcriptional response of Citrus aurantifolia to infection by Citrus
tristeza virus},
author = { M. Gandia and A. Conesa and G. Ancillo and J. Gadea and J. Forment and V. Pallas and R. Flores and N. Duran-Vila and P. Moreno and J. Guerri},
url = {http://dx.doi.org/10.1016/j.virol.2007.05.025},
doi = {10.1016/j.virol.2007.05.025},
issn = {0042-6822},
year = {2007},
date = {2007-10-01},
journal = {VIROLOGY},
volume = {367},
number = {2},
pages = {298-306},
abstract = {Changes in gene expression of Mexican lime plants in response to
infection with a severe (T305) or a mild (T385) isolate of Citrus
tristeza virus (CTV) were analyzed using a cDNA microarray containing
12,672 probes to 6875 different citrus genes. Statistically significant
(P < 0.01) expression changes of 334 genes were detected in response to
infection with isolate T305, whereas infection with T385 induced no
significant change. Induced genes included 145 without significant
similarity with known sequences and 189 that were classified in seven
functional categories. Genes related with response to stress and defense
were the main category and included 28% of the genes induced. Selected
transcription changes detected by microarray analysis were confirmed by
quantitative real-time RT-PCR. Changes detected in the transcriptome
upon infecting lime with T305 may be associated either with symptom
expression, with a strain-specific defense mechanism, or with a general
response to stress. (c) 2007 Elsevier Inc. All rights reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Changes in gene expression of Mexican lime plants in response to
infection with a severe (T305) or a mild (T385) isolate of Citrus
tristeza virus (CTV) were analyzed using a cDNA microarray containing
12,672 probes to 6875 different citrus genes. Statistically significant
(P < 0.01) expression changes of 334 genes were detected in response to
infection with isolate T305, whereas infection with T385 induced no
significant change. Induced genes included 145 without significant
similarity with known sequences and 189 that were classified in seven
functional categories. Genes related with response to stress and defense
were the main category and included 28% of the genes induced. Selected
transcription changes detected by microarray analysis were confirmed by
quantitative real-time RT-PCR. Changes detected in the transcriptome
upon infecting lime with T305 may be associated either with symptom
expression, with a strain-specific defense mechanism, or with a general
response to stress. (c) 2007 Elsevier Inc. All rights reserved.
infection with a severe (T305) or a mild (T385) isolate of Citrus
tristeza virus (CTV) were analyzed using a cDNA microarray containing
12,672 probes to 6875 different citrus genes. Statistically significant
(P < 0.01) expression changes of 334 genes were detected in response to
infection with isolate T305, whereas infection with T385 induced no
significant change. Induced genes included 145 without significant
similarity with known sequences and 189 that were classified in seven
functional categories. Genes related with response to stress and defense
were the main category and included 28% of the genes induced. Selected
transcription changes detected by microarray analysis were confirmed by
quantitative real-time RT-PCR. Changes detected in the transcriptome
upon infecting lime with T305 may be associated either with symptom
expression, with a strain-specific defense mechanism, or with a general
response to stress. (c) 2007 Elsevier Inc. All rights reserved.
14.
Nueda, M. J.; Conesa, A.; Westerhuis, J. A.; Hoefsloot, H. C. J.; Smilde, A. K.; Talon, M.; Ferrer, A.
Discovering gene expression patterns in time course microarray experiments by ANOVA-SCA Journal Article
In: BIOINFORMATICS, vol. 23, no. 14, pp. 1792-1800, 2007, ISSN: 1367-4803.
@article{ISI:000249248300011,
title = {Discovering gene expression patterns in time course microarray
experiments by ANOVA-SCA},
author = { M. J. Nueda and A. Conesa and J. A. Westerhuis and H. C. J. Hoefsloot and A. K. Smilde and M. Talon and A. Ferrer},
url = {http://dx.doi.org/10.1093/bioinformatics/btm251},
doi = {10.1093/bioinformatics/btm251},
issn = {1367-4803},
year = {2007},
date = {2007-07-01},
journal = {BIOINFORMATICS},
volume = {23},
number = {14},
pages = {1792-1800},
abstract = {Motivation: Designed microarray experiments are used to investigate the
effects that controlled experimental factors have on gene expression and
learn about the transcriptional responses associated with external
variables. In these datasets, signals of interest coexist with varying
sources of unwanted noise in a framework of (co)relation among the
measured variables and with the different levels of the studied factors.
Discovering experimentally relevant transcriptional changes require
methodologies that take all these elements into account.
Results: In this work, we develop the application of the Analysis of
variance-simultaneous component analysis (ANOVA-SCA) Smilde et al, Bioinformatics, (2005) to the analysis of multiple series time course
microarray data as an example of multifactorial gene expression
profiling experiments. We denoted this implementation as ASCA-genes. We
show how the combination of ANOVA-modeling and a dimension reduction
technique is effective in extracting targeted signals from data
by-passing structural noise. The methodology is valuable for identifying
main and secondary responses associated with the experimental factors
and spotting relevant experimental conditions. We additionally propose a
novel approach for gene selection in the context of the relation of
individual transcriptional patterns to global gene expression signals.
We demonstrate the methodology on both real and synthetic datasets.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Motivation: Designed microarray experiments are used to investigate the
effects that controlled experimental factors have on gene expression and
learn about the transcriptional responses associated with external
variables. In these datasets, signals of interest coexist with varying
sources of unwanted noise in a framework of (co)relation among the
measured variables and with the different levels of the studied factors.
Discovering experimentally relevant transcriptional changes require
methodologies that take all these elements into account.
Results: In this work, we develop the application of the Analysis of
variance-simultaneous component analysis (ANOVA-SCA) Smilde et al, Bioinformatics, (2005) to the analysis of multiple series time course
microarray data as an example of multifactorial gene expression
profiling experiments. We denoted this implementation as ASCA-genes. We
show how the combination of ANOVA-modeling and a dimension reduction
technique is effective in extracting targeted signals from data
by-passing structural noise. The methodology is valuable for identifying
main and secondary responses associated with the experimental factors
and spotting relevant experimental conditions. We additionally propose a
novel approach for gene selection in the context of the relation of
individual transcriptional patterns to global gene expression signals.
We demonstrate the methodology on both real and synthetic datasets.
effects that controlled experimental factors have on gene expression and
learn about the transcriptional responses associated with external
variables. In these datasets, signals of interest coexist with varying
sources of unwanted noise in a framework of (co)relation among the
measured variables and with the different levels of the studied factors.
Discovering experimentally relevant transcriptional changes require
methodologies that take all these elements into account.
Results: In this work, we develop the application of the Analysis of
variance-simultaneous component analysis (ANOVA-SCA) Smilde et al, Bioinformatics, (2005) to the analysis of multiple series time course
microarray data as an example of multifactorial gene expression
profiling experiments. We denoted this implementation as ASCA-genes. We
show how the combination of ANOVA-modeling and a dimension reduction
technique is effective in extracting targeted signals from data
by-passing structural noise. The methodology is valuable for identifying
main and secondary responses associated with the experimental factors
and spotting relevant experimental conditions. We additionally propose a
novel approach for gene selection in the context of the relation of
individual transcriptional patterns to global gene expression signals.
We demonstrate the methodology on both real and synthetic datasets.
13.
Terol, J.; Conesa, A.; Colmenero, J. M.; Cercos, M.; Tadeo, F.; Agusti, J.; Alos, E.; Andres, F.; Soler, G.; Brumos, J.; Iglesias, D. J.; Gotz, S.; Legaz, F.; Argout, X.; Courtois, B.; Ollitrault, P.; Dossat, C.; Wincker, P.; Morillon, R.; Talon, M.
Analysis of 13000 unique Citrus clusters associated with fruit quality, production and salinity tolerance Journal Article
In: BMC GENOMICS, vol. 8, 2007, ISSN: 1471-2164.
@article{ISI:000244326200001,
title = {Analysis of 13000 unique Citrus clusters associated with fruit quality, production and salinity tolerance},
author = { J. Terol and A. Conesa and J. M. Colmenero and M. Cercos and F. Tadeo and J. Agusti and E. Alos and F. Andres and G. Soler and J. Brumos and D. J. Iglesias and S. Gotz and F. Legaz and X. Argout and B. Courtois and P. Ollitrault and C. Dossat and P. Wincker and R. Morillon and M. Talon},
url = {http://dx.doi.org/10.1186/1471-2164-8-31},
doi = {10.1186/1471-2164-8-31},
issn = {1471-2164},
year = {2007},
date = {2007-01-01},
journal = {BMC GENOMICS},
volume = {8},
abstract = {Background: Improvement of Citrus, the most economically important fruit
crop in the world, is extremely slow and inherently costly because of
the long-term nature of tree breeding and an unusual combination of
reproductive characteristics. Aside from disease resistance, major
commercial traits in Citrus are improved fruit quality, higher yield and
tolerance to environmental stresses, especially salinity.
Results: A normalized full length and 9 standard cDNA libraries were
generated, representing particular treatments and tissues from selected
varieties ( Citrus clementina and C. sinensis) and rootstocks ( C.
reshni, and C. sinenis x Poncirus trifoliata) differing in fruit
quality, resistance to abscission, and tolerance to salinity. The goal
of this work was to provide a large expressed sequence tag ( EST)
collection enriched with transcripts related to these well appreciated
agronomical traits. Towards this end, more than 54000 ESTs derived from
these libraries were analyzed and annotated. Assembly of 52626 useful
sequences generated 15664 putative transcription units distributed in
7120 contigs, and 8544 singletons. BLAST annotation produced significant
hits for more than 80% of the hypothetical transcription units and
suggested that 647 of these might be Citrus specific unigenes. The
unigene set, composed of similar to 13000 putative different
transcripts, including more than 5000 novel Citrus genes, was assigned
with putative functions based on similarity, GO annotations and protein
domains.
Conclusion: Comparative genomics with Arabidopsis revealed the presence
of putative conserved orthologs and single copy genes in Citrus and also
the occurrence of both gene duplication events and increased number of
genes for specific pathways. In addition, phylogenetic analysis
performed on the ammonium transporter family and glycosyl transferase
family 20 suggested the existence of Citrus paralogs. Analysis of the
Citrus gene space showed that the most important metabolic pathways
known to affect fruit quality were represented in the unigene set.
Overall, the similarity analyses indicated that the sequences of the
genes belonging to these varieties and rootstocks were essentially
identical, suggesting that the differential behaviour of these species
cannot be attributed to major sequence divergences. This Citrus EST
assembly contributes both crucial information to discover genes of
agronomical interest and tools for genetic and genomic analyses, such as
the development of new markers and microarrays.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Improvement of Citrus, the most economically important fruit
crop in the world, is extremely slow and inherently costly because of
the long-term nature of tree breeding and an unusual combination of
reproductive characteristics. Aside from disease resistance, major
commercial traits in Citrus are improved fruit quality, higher yield and
tolerance to environmental stresses, especially salinity.
Results: A normalized full length and 9 standard cDNA libraries were
generated, representing particular treatments and tissues from selected
varieties ( Citrus clementina and C. sinensis) and rootstocks ( C.
reshni, and C. sinenis x Poncirus trifoliata) differing in fruit
quality, resistance to abscission, and tolerance to salinity. The goal
of this work was to provide a large expressed sequence tag ( EST)
collection enriched with transcripts related to these well appreciated
agronomical traits. Towards this end, more than 54000 ESTs derived from
these libraries were analyzed and annotated. Assembly of 52626 useful
sequences generated 15664 putative transcription units distributed in
7120 contigs, and 8544 singletons. BLAST annotation produced significant
hits for more than 80% of the hypothetical transcription units and
suggested that 647 of these might be Citrus specific unigenes. The
unigene set, composed of similar to 13000 putative different
transcripts, including more than 5000 novel Citrus genes, was assigned
with putative functions based on similarity, GO annotations and protein
domains.
Conclusion: Comparative genomics with Arabidopsis revealed the presence
of putative conserved orthologs and single copy genes in Citrus and also
the occurrence of both gene duplication events and increased number of
genes for specific pathways. In addition, phylogenetic analysis
performed on the ammonium transporter family and glycosyl transferase
family 20 suggested the existence of Citrus paralogs. Analysis of the
Citrus gene space showed that the most important metabolic pathways
known to affect fruit quality were represented in the unigene set.
Overall, the similarity analyses indicated that the sequences of the
genes belonging to these varieties and rootstocks were essentially
identical, suggesting that the differential behaviour of these species
cannot be attributed to major sequence divergences. This Citrus EST
assembly contributes both crucial information to discover genes of
agronomical interest and tools for genetic and genomic analyses, such as
the development of new markers and microarrays.
crop in the world, is extremely slow and inherently costly because of
the long-term nature of tree breeding and an unusual combination of
reproductive characteristics. Aside from disease resistance, major
commercial traits in Citrus are improved fruit quality, higher yield and
tolerance to environmental stresses, especially salinity.
Results: A normalized full length and 9 standard cDNA libraries were
generated, representing particular treatments and tissues from selected
varieties ( Citrus clementina and C. sinensis) and rootstocks ( C.
reshni, and C. sinenis x Poncirus trifoliata) differing in fruit
quality, resistance to abscission, and tolerance to salinity. The goal
of this work was to provide a large expressed sequence tag ( EST)
collection enriched with transcripts related to these well appreciated
agronomical traits. Towards this end, more than 54000 ESTs derived from
these libraries were analyzed and annotated. Assembly of 52626 useful
sequences generated 15664 putative transcription units distributed in
7120 contigs, and 8544 singletons. BLAST annotation produced significant
hits for more than 80% of the hypothetical transcription units and
suggested that 647 of these might be Citrus specific unigenes. The
unigene set, composed of similar to 13000 putative different
transcripts, including more than 5000 novel Citrus genes, was assigned
with putative functions based on similarity, GO annotations and protein
domains.
Conclusion: Comparative genomics with Arabidopsis revealed the presence
of putative conserved orthologs and single copy genes in Citrus and also
the occurrence of both gene duplication events and increased number of
genes for specific pathways. In addition, phylogenetic analysis
performed on the ammonium transporter family and glycosyl transferase
family 20 suggested the existence of Citrus paralogs. Analysis of the
Citrus gene space showed that the most important metabolic pathways
known to affect fruit quality were represented in the unigene set.
Overall, the similarity analyses indicated that the sequences of the
genes belonging to these varieties and rootstocks were essentially
identical, suggesting that the differential behaviour of these species
cannot be attributed to major sequence divergences. This Citrus EST
assembly contributes both crucial information to discover genes of
agronomical interest and tools for genetic and genomic analyses, such as
the development of new markers and microarrays.
2006
12.
Williams, T. D.; Diab, A. M.; George, S. G.; Godfrey, R. E.; Sabine, V.; Conesa, A.; Minchin, S. D.; Watts, P. C.; Chipman, J. K.
In: ENVIRONMENTAL SCIENCE & TECHNOLOGY, vol. 40, no. 20, pp. 6479-6488, 2006, ISSN: 0013-936X.
@article{ISI:000241192600050,
title = {Development of the GENIPOL European flounder (Platichthys flesus)
microarray and determination of temporal transcriptional responses to
cadmium at low dose.},
author = { T. D. Williams and A. M. Diab and S. G. George and R. E. Godfrey and V. Sabine and A. Conesa and S. D. Minchin and P. C. Watts and J. K. Chipman},
url = {http://dx.doi.org/10.1021/es061142h},
doi = {10.1021/es061142h},
issn = {0013-936X},
year = {2006},
date = {2006-10-01},
journal = {ENVIRONMENTAL SCIENCE & TECHNOLOGY},
volume = {40},
number = {20},
pages = {6479-6488},
abstract = {We have constructed a high density, 13 270-clone cDNA array for the
sentinel fish species European flounder (Platichthys flesus), combining
clones from suppressive subtractive hybridization and a liver cDNA
library; DNA sequences of 5211 clones were determined. Fish were treated
by single intraperitoneal injection with 50 micrograms cadmium chloride
per kilogram body weight, a dose relevant to environmental exposures, and hepatic gene expression changes were determined at 1, 2, 4, 8, and
16 days postinjection in comparison to saline-treated controls. Gene
expression responses were confirmed by real-time reverse transcription
polymerase chain reaction (RT-PCR). Blast2GO gene ontology analysis
highlighted a general induction of the unfolded protein response, response to oxidative stress, protein synthesis, transport, and
degradation pathways, while apoptosis, cell cycle, cytoskeleton, and
cytokine genes were also affected. Transcript levels of cytochrome P450
1A (CYP1A) were repressed and vitellogenin altered, real-time PCR showed
induction of metallothionein. We thus describe the establishment of a
useful resource for ecotoxicogenomics and the determination of the
temporal molecular responses to cadmium, a prototypical heavy metal
pollutant.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We have constructed a high density, 13 270-clone cDNA array for the
sentinel fish species European flounder (Platichthys flesus), combining
clones from suppressive subtractive hybridization and a liver cDNA
library; DNA sequences of 5211 clones were determined. Fish were treated
by single intraperitoneal injection with 50 micrograms cadmium chloride
per kilogram body weight, a dose relevant to environmental exposures, and hepatic gene expression changes were determined at 1, 2, 4, 8, and
16 days postinjection in comparison to saline-treated controls. Gene
expression responses were confirmed by real-time reverse transcription
polymerase chain reaction (RT-PCR). Blast2GO gene ontology analysis
highlighted a general induction of the unfolded protein response, response to oxidative stress, protein synthesis, transport, and
degradation pathways, while apoptosis, cell cycle, cytoskeleton, and
cytokine genes were also affected. Transcript levels of cytochrome P450
1A (CYP1A) were repressed and vitellogenin altered, real-time PCR showed
induction of metallothionein. We thus describe the establishment of a
useful resource for ecotoxicogenomics and the determination of the
temporal molecular responses to cadmium, a prototypical heavy metal
pollutant.
sentinel fish species European flounder (Platichthys flesus), combining
clones from suppressive subtractive hybridization and a liver cDNA
library; DNA sequences of 5211 clones were determined. Fish were treated
by single intraperitoneal injection with 50 micrograms cadmium chloride
per kilogram body weight, a dose relevant to environmental exposures, and hepatic gene expression changes were determined at 1, 2, 4, 8, and
16 days postinjection in comparison to saline-treated controls. Gene
expression responses were confirmed by real-time reverse transcription
polymerase chain reaction (RT-PCR). Blast2GO gene ontology analysis
highlighted a general induction of the unfolded protein response, response to oxidative stress, protein synthesis, transport, and
degradation pathways, while apoptosis, cell cycle, cytoskeleton, and
cytokine genes were also affected. Transcript levels of cytochrome P450
1A (CYP1A) were repressed and vitellogenin altered, real-time PCR showed
induction of metallothionein. We thus describe the establishment of a
useful resource for ecotoxicogenomics and the determination of the
temporal molecular responses to cadmium, a prototypical heavy metal
pollutant.
11.
Conesa, A.; Nueda, M.; Ferrer, A.; Talon, M.
maSigPro: a method to identify significantly differential expression profiles in time-course microarray experiments Journal Article
In: BIOINFORMATICS, vol. 22, no. 9, pp. 1096-1102, 2006, ISSN: 1367-4803.
@article{ISI:000236997600009,
title = {maSigPro: a method to identify significantly differential expression
profiles in time-course microarray experiments},
author = { A. Conesa and M. Nueda and A. Ferrer and M. Talon},
url = {http://dx.doi.org/10.1093/bioinformatics/btl056},
doi = {10.1093/bioinformatics/btl056},
issn = {1367-4803},
year = {2006},
date = {2006-05-01},
journal = {BIOINFORMATICS},
volume = {22},
number = {9},
pages = {1096-1102},
abstract = {Motivation: Multi-series time-course microarray experiments are useful
approaches for exploring biological processes. In this type of
experiments, the researcher is frequently interested in studying gene
expression changes along time and in evaluating trend differences
between the various experimental groups. The large amount of data, multiplicity of experimental conditions and the dynamic nature of the
experiments poses great challenges to data analysis.
Results: In this work, we propose a statistical procedure to identify
genes that show different gene expression profiles across analytical
groups in time-course experiments. The method is a two-regression step
approach where the experimental groups are identified by dummy
variables. The procedure first adjusts a global regression model with
all the defined variables to identify differentially expressed genes, and in second a variable selection strategy is applied to study
differences between groups and to find statistically significant
different profiles. The methodology is illustrated on both a real and a
simulated microarray dataset.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Motivation: Multi-series time-course microarray experiments are useful
approaches for exploring biological processes. In this type of
experiments, the researcher is frequently interested in studying gene
expression changes along time and in evaluating trend differences
between the various experimental groups. The large amount of data, multiplicity of experimental conditions and the dynamic nature of the
experiments poses great challenges to data analysis.
Results: In this work, we propose a statistical procedure to identify
genes that show different gene expression profiles across analytical
groups in time-course experiments. The method is a two-regression step
approach where the experimental groups are identified by dummy
variables. The procedure first adjusts a global regression model with
all the defined variables to identify differentially expressed genes, and in second a variable selection strategy is applied to study
differences between groups and to find statistically significant
different profiles. The methodology is illustrated on both a real and a
simulated microarray dataset.
approaches for exploring biological processes. In this type of
experiments, the researcher is frequently interested in studying gene
expression changes along time and in evaluating trend differences
between the various experimental groups. The large amount of data, multiplicity of experimental conditions and the dynamic nature of the
experiments poses great challenges to data analysis.
Results: In this work, we propose a statistical procedure to identify
genes that show different gene expression profiles across analytical
groups in time-course experiments. The method is a two-regression step
approach where the experimental groups are identified by dummy
variables. The procedure first adjusts a global regression model with
all the defined variables to identify differentially expressed genes, and in second a variable selection strategy is applied to study
differences between groups and to find statistically significant
different profiles. The methodology is illustrated on both a real and a
simulated microarray dataset.
2005
10.
Conesa, A.; Gotz, S.; Garcia-Gomez, J.; Terol, J.; Talon, M.; Robles, M.
Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research Journal Article
In: BIOINFORMATICS, vol. 21, no. 18, pp. 3674-3676, 2005, ISSN: 1367-4803.
@article{ISI:000231694600016,
title = {Blast2GO: a universal tool for annotation, visualization and analysis in
functional genomics research},
author = { A. Conesa and S. Gotz and J. Garcia-Gomez and J. Terol and M. Talon and M. Robles},
url = {http://dx.doi.org/10.1093/bioinformatics/bti610},
doi = {10.1093/bioinformatics/bti610},
issn = {1367-4803},
year = {2005},
date = {2005-09-01},
journal = {BIOINFORMATICS},
volume = {21},
number = {18},
pages = {3674-3676},
abstract = {We present here Blast2GO (B2G), a research tool designed with the main
purpose of enabling Gene Ontology (GO) based data mining on sequence
data for which no GO annotation is yet available. B2G joints in one
application GO annotation based on similarity searches with statistical
analysis and highlighted visualization on directed acyclic graphs. This
tool offers a suitable platform for functional genomics research in
non-model species. B2G is an intuitive and interactive desktop
application that allows monitoring and comprehension of the whole
annotation and analysis process.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We present here Blast2GO (B2G), a research tool designed with the main
purpose of enabling Gene Ontology (GO) based data mining on sequence
data for which no GO annotation is yet available. B2G joints in one
application GO annotation based on similarity searches with statistical
analysis and highlighted visualization on directed acyclic graphs. This
tool offers a suitable platform for functional genomics research in
non-model species. B2G is an intuitive and interactive desktop
application that allows monitoring and comprehension of the whole
annotation and analysis process.
purpose of enabling Gene Ontology (GO) based data mining on sequence
data for which no GO annotation is yet available. B2G joints in one
application GO annotation based on similarity searches with statistical
analysis and highlighted visualization on directed acyclic graphs. This
tool offers a suitable platform for functional genomics research in
non-model species. B2G is an intuitive and interactive desktop
application that allows monitoring and comprehension of the whole
annotation and analysis process.
9.
Forment, J.; Gadea, J.; Huerta, L.; Abizanda, L.; Agusti, J.; Alamar, S.; Alos, E.; Andres, F.; Arribas, R.; Beltran, J.; Berbel, A.; Blazquez, M.; Brumos, J.; Canas, L.; Cercos, M.; Colmenero-Flores, J.; Conesa, A.; Estables, B.; Gandia, M.; Garcia-Martinez, J.; Gimeno, J.; Gisbert, A.; Gomez, G.; Gonzalez-Candelas, L.; Granell, A.; Guerri, J.; Lafuente, M.; Madueno, F.; Marcos, J.; Marques, M.; Martinez, F.; Martinez-Godoy, M.; Miralles, S.; Moreno, P.; Navarro, L.; Pallas, V.; Perez-Amador, M.; Perez-Valle, J.; Pons, C.; Rodrigo, I.; Rodriguez, P.; Royo, C.; Serrano, R.; Soler, G.; Tadeo, F.; Talon, M.; Terol, J.; Trenor, M.; Vaello, L.; Vicente, O.; Vidal, C.; Zacarias, L.; Conejero, V.
Development of a citrus genome-wide EST collection and cDNA microarray as resources for genomic studies Journal Article
In: PLANT MOLECULAR BIOLOGY, vol. 57, no. 3, pp. 375-391, 2005, ISSN: 0167-4412.
@article{ISI:000229478400005,
title = {Development of a citrus genome-wide EST collection and cDNA microarray
as resources for genomic studies},
author = { J. Forment and J. Gadea and L. Huerta and L. Abizanda and J. Agusti and S. Alamar and E. Alos and F. Andres and R. Arribas and J. Beltran and A. Berbel and M. Blazquez and J. Brumos and L. Canas and M. Cercos and J. Colmenero-Flores and A. Conesa and B. Estables and M. Gandia and J. Garcia-Martinez and J. Gimeno and A. Gisbert and G. Gomez and L. Gonzalez-Candelas and A. Granell and J. Guerri and M. Lafuente and F. Madueno and J. Marcos and M. Marques and F. Martinez and M. Martinez-Godoy and S. Miralles and P. Moreno and L. Navarro and V. Pallas and M. Perez-Amador and J. Perez-Valle and C. Pons and I. Rodrigo and P. Rodriguez and C. Royo and R. Serrano and G. Soler and F. Tadeo and M. Talon and J. Terol and M. Trenor and L. Vaello and O. Vicente and C. Vidal and L. Zacarias and V. Conejero},
url = {http://dx.doi.org/10.1007/s11103-004-7926-1},
doi = {10.1007/s11103-004-7926-1},
issn = {0167-4412},
year = {2005},
date = {2005-02-01},
journal = {PLANT MOLECULAR BIOLOGY},
volume = {57},
number = {3},
pages = {375-391},
abstract = {A functional genomics project has been initiated to approach the
molecular characterization of the main biological and agronomical traits
of citrus. As a key part of this project, a citrus EST collection has
been generated from 25 cDNA libraries covering different tissues, developmental stages and stress conditions. The collection includes a
total of 22,635 high-quality ESTs, grouped in 11,836 putative unigenes, which represent at least one third of the estimated number of genes in
the citrus genome. Functional annotation of unigenes which have
Arabidopsis orthologues (68% of all unigenes) revealed gene
representation in every major functional category, suggesting that a
genome-wide EST collection was obtained. A Citrus clementina Hort. ex
Tan. cv. Clemenules genomic library, that will contribute to further
characterization of relevant genes, has also been constructed. To
initiate the analysis of citrus transcriptome, we have developed a cDNA
microarray containing 12,672 probes corresponding to 6875 putative
unigenes of the collection. Technical characterization of the microarray
showed high intra- and inter-array reproducibility, as well as a good
range of sensitivity. We have also validated gene expression data
achieved with this microarray through an independent technique such as
RNA gel blot analysis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A functional genomics project has been initiated to approach the
molecular characterization of the main biological and agronomical traits
of citrus. As a key part of this project, a citrus EST collection has
been generated from 25 cDNA libraries covering different tissues, developmental stages and stress conditions. The collection includes a
total of 22,635 high-quality ESTs, grouped in 11,836 putative unigenes, which represent at least one third of the estimated number of genes in
the citrus genome. Functional annotation of unigenes which have
Arabidopsis orthologues (68% of all unigenes) revealed gene
representation in every major functional category, suggesting that a
genome-wide EST collection was obtained. A Citrus clementina Hort. ex
Tan. cv. Clemenules genomic library, that will contribute to further
characterization of relevant genes, has also been constructed. To
initiate the analysis of citrus transcriptome, we have developed a cDNA
microarray containing 12,672 probes corresponding to 6875 putative
unigenes of the collection. Technical characterization of the microarray
showed high intra- and inter-array reproducibility, as well as a good
range of sensitivity. We have also validated gene expression data
achieved with this microarray through an independent technique such as
RNA gel blot analysis.
molecular characterization of the main biological and agronomical traits
of citrus. As a key part of this project, a citrus EST collection has
been generated from 25 cDNA libraries covering different tissues, developmental stages and stress conditions. The collection includes a
total of 22,635 high-quality ESTs, grouped in 11,836 putative unigenes, which represent at least one third of the estimated number of genes in
the citrus genome. Functional annotation of unigenes which have
Arabidopsis orthologues (68% of all unigenes) revealed gene
representation in every major functional category, suggesting that a
genome-wide EST collection was obtained. A Citrus clementina Hort. ex
Tan. cv. Clemenules genomic library, that will contribute to further
characterization of relevant genes, has also been constructed. To
initiate the analysis of citrus transcriptome, we have developed a cDNA
microarray containing 12,672 probes corresponding to 6875 putative
unigenes of the collection. Technical characterization of the microarray
showed high intra- and inter-array reproducibility, as well as a good
range of sensitivity. We have also validated gene expression data
achieved with this microarray through an independent technique such as
RNA gel blot analysis.
2003
8.
Yi, X.; Conesa, A.; Punt, P.; Hager, L.
Examining the role of glutamic acid 183 in chloroperoxidase catalysis Journal Article
In: JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 278, no. 16, pp. 13855-13859, 2003, ISSN: 0021-9258.
@article{ISI:000182405000038,
title = {Examining the role of glutamic acid 183 in chloroperoxidase catalysis},
author = { X. Yi and A. Conesa and P. Punt and L. Hager},
url = {http://dx.doi.org/10.1074/jbc.M210906200},
doi = {10.1074/jbc.M210906200},
issn = {0021-9258},
year = {2003},
date = {2003-04-01},
journal = {JOURNAL OF BIOLOGICAL CHEMISTRY},
volume = {278},
number = {16},
pages = {13855-13859},
abstract = {Site-directed mutagenesis has been used to investigate the role of
glutamic acid 183 in chloroperoxidase catalysis. Based on the x-ray
crystallographic structure of chloroperoxidase, Glu-183 is postulated to
function on distal side of the heme prosthetic group as an acid-base
catalyst in facilitating the reaction between the peroxidase and
hydrogen peroxide with the formation of Compound I. In contrast, the
other members of the heme peroxidase family use a histidine residue in
this role. Plasmids have now been constructed in which the codon for
Glu-183 is replaced with a histidine codon. The mutant recombinant gene
has been expressed in Aspergillus niger. An analysis of the produced
mutant gene shows that the substitution of Glu-183 with a His residue is
detrimental to the chlorination and dismutation activity of
chloroperoxidase. The activity is reduced by 85 and 50% of wild type
activity, respectively. However, quite unexpectedly, the epoxidation
activity of the mutant enzyme is significantly enhanced similar
to2.5-fold. These results show that Glu-183 is important but not
essential for the chlorination activity of chloroperoxidase. It is
possible that the increased epoxidation of the mutant enzyme is based on
an increase in the hydrophobicity of the active site.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Site-directed mutagenesis has been used to investigate the role of
glutamic acid 183 in chloroperoxidase catalysis. Based on the x-ray
crystallographic structure of chloroperoxidase, Glu-183 is postulated to
function on distal side of the heme prosthetic group as an acid-base
catalyst in facilitating the reaction between the peroxidase and
hydrogen peroxide with the formation of Compound I. In contrast, the
other members of the heme peroxidase family use a histidine residue in
this role. Plasmids have now been constructed in which the codon for
Glu-183 is replaced with a histidine codon. The mutant recombinant gene
has been expressed in Aspergillus niger. An analysis of the produced
mutant gene shows that the substitution of Glu-183 with a His residue is
detrimental to the chlorination and dismutation activity of
chloroperoxidase. The activity is reduced by 85 and 50% of wild type
activity, respectively. However, quite unexpectedly, the epoxidation
activity of the mutant enzyme is significantly enhanced similar
to2.5-fold. These results show that Glu-183 is important but not
essential for the chlorination activity of chloroperoxidase. It is
possible that the increased epoxidation of the mutant enzyme is based on
an increase in the hydrophobicity of the active site.
glutamic acid 183 in chloroperoxidase catalysis. Based on the x-ray
crystallographic structure of chloroperoxidase, Glu-183 is postulated to
function on distal side of the heme prosthetic group as an acid-base
catalyst in facilitating the reaction between the peroxidase and
hydrogen peroxide with the formation of Compound I. In contrast, the
other members of the heme peroxidase family use a histidine residue in
this role. Plasmids have now been constructed in which the codon for
Glu-183 is replaced with a histidine codon. The mutant recombinant gene
has been expressed in Aspergillus niger. An analysis of the produced
mutant gene shows that the substitution of Glu-183 with a His residue is
detrimental to the chlorination and dismutation activity of
chloroperoxidase. The activity is reduced by 85 and 50% of wild type
activity, respectively. However, quite unexpectedly, the epoxidation
activity of the mutant enzyme is significantly enhanced similar
to2.5-fold. These results show that Glu-183 is important but not
essential for the chlorination activity of chloroperoxidase. It is
possible that the increased epoxidation of the mutant enzyme is based on
an increase in the hydrophobicity of the active site.
2002
7.
Punt, P.; van Biezen, N.; Conesa, A.; Albers, A.; Mangnus, J.; van den Hondel, C.
Filamentous fungi as cell factories for heterologous protein production Journal Article
In: TRENDS IN BIOTECHNOLOGY, vol. 20, no. 5, pp. 200-206, 2002, ISSN: 0167-7799.
@article{ISI:000175065300008,
title = {Filamentous fungi as cell factories for heterologous protein production},
author = { P. Punt and N. van Biezen and A. Conesa and A. Albers and J. Mangnus and C. van den Hondel},
url = {http://dx.doi.org/10.1016/S0167-7799(02)01933-9},
doi = {10.1016/S0167-7799(02)01933-9},
issn = {0167-7799},
year = {2002},
date = {2002-05-01},
journal = {TRENDS IN BIOTECHNOLOGY},
volume = {20},
number = {5},
pages = {200-206},
abstract = {Filamentous fungi have been used as sources of metabolites and enzymes
for centuries. For about two decades, molecular genetic tools have
enabled us to use these organisms to express extra copies of both
endogenous and exogenous genes. This review of current practice reveals
that molecular tools have enabled several new developments. But it has
been process development that has driven the final breakthrough to
achieving commercially relevant quantities of protein. Recent research
into gene expression in filamentous fungi has explored their wealth of
genetic diversity with a view to exploiting them as expression hosts and
as a source of new genes. Inevitably, the progress in the `genomics'
technology will further develop high-throughput technologies for these
organisms.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Filamentous fungi have been used as sources of metabolites and enzymes
for centuries. For about two decades, molecular genetic tools have
enabled us to use these organisms to express extra copies of both
endogenous and exogenous genes. This review of current practice reveals
that molecular tools have enabled several new developments. But it has
been process development that has driven the final breakthrough to
achieving commercially relevant quantities of protein. Recent research
into gene expression in filamentous fungi has explored their wealth of
genetic diversity with a view to exploiting them as expression hosts and
as a source of new genes. Inevitably, the progress in the `genomics'
technology will further develop high-throughput technologies for these
organisms.
for centuries. For about two decades, molecular genetic tools have
enabled us to use these organisms to express extra copies of both
endogenous and exogenous genes. This review of current practice reveals
that molecular tools have enabled several new developments. But it has
been process development that has driven the final breakthrough to
achieving commercially relevant quantities of protein. Recent research
into gene expression in filamentous fungi has explored their wealth of
genetic diversity with a view to exploiting them as expression hosts and
as a source of new genes. Inevitably, the progress in the `genomics'
technology will further develop high-throughput technologies for these
organisms.
6.
Conesa, A.; Punt, P.; van den Hondel, C.
Fungal peroxidases: molecular aspects and applications Journal Article
In: JOURNAL OF BIOTECHNOLOGY, vol. 93, no. 2, pp. 143-158, 2002, ISSN: 0168-1656.
@article{ISI:000173535800005,
title = {Fungal peroxidases: molecular aspects and applications},
author = { A. Conesa and P. Punt and C. van den Hondel},
url = {http://dx.doi.org/10.1016/S0168-1656(01)00394-7},
doi = {10.1016/S0168-1656(01)00394-7},
issn = {0168-1656},
year = {2002},
date = {2002-02-01},
journal = {JOURNAL OF BIOTECHNOLOGY},
volume = {93},
number = {2},
pages = {143-158},
abstract = {Peroxidases are oxidoreductases that utilize hydrogen peroxide to
catalyze oxidative reactions. A large number of peroxidases have been
identified in fungal species and are being characterized at the
molecular level. In this manuscript we review the current knowledge on
the molecular aspects of this type of enzymes. We present an overview of
the research efforts undertaken in deciphering the structural basis of
the catalytic properties of fungal peroxidases and discuss molecular
genetics and protein homology aspects of this enzyme class. Finally, we
summarize the potential biotechnological applications of these enzymes
and evaluate recent advances on their expression in heterologous systems
for production purposes. (C) 2002 Elsevier Science B.V. All rights
reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Peroxidases are oxidoreductases that utilize hydrogen peroxide to
catalyze oxidative reactions. A large number of peroxidases have been
identified in fungal species and are being characterized at the
molecular level. In this manuscript we review the current knowledge on
the molecular aspects of this type of enzymes. We present an overview of
the research efforts undertaken in deciphering the structural basis of
the catalytic properties of fungal peroxidases and discuss molecular
genetics and protein homology aspects of this enzyme class. Finally, we
summarize the potential biotechnological applications of these enzymes
and evaluate recent advances on their expression in heterologous systems
for production purposes. (C) 2002 Elsevier Science B.V. All rights
reserved.
catalyze oxidative reactions. A large number of peroxidases have been
identified in fungal species and are being characterized at the
molecular level. In this manuscript we review the current knowledge on
the molecular aspects of this type of enzymes. We present an overview of
the research efforts undertaken in deciphering the structural basis of
the catalytic properties of fungal peroxidases and discuss molecular
genetics and protein homology aspects of this enzyme class. Finally, we
summarize the potential biotechnological applications of these enzymes
and evaluate recent advances on their expression in heterologous systems
for production purposes. (C) 2002 Elsevier Science B.V. All rights
reserved.
5.
Conesa, A.; Jeenes, D.; Archer, D.; van den Hondel, C.; Punt, P.
Calnexin overexpression increases manganese peroxidase production in Aspergillus niger Journal Article
In: APPLIED AND ENVIRONMENTAL MICROBIOLOGY, vol. 68, no. 2, pp. 846-851, 2002, ISSN: 0099-2240.
@article{ISI:000173588600051,
title = {Calnexin overexpression increases manganese peroxidase production in
Aspergillus niger},
author = { A. Conesa and D. Jeenes and D. Archer and C. van den Hondel and P. Punt},
url = {http://dx.doi.org/10.1128/AEM.68.2.846-851.2002},
doi = {10.1128/AEM.68.2.846-851.2002},
issn = {0099-2240},
year = {2002},
date = {2002-02-01},
journal = {APPLIED AND ENVIRONMENTAL MICROBIOLOGY},
volume = {68},
number = {2},
pages = {846-851},
abstract = {Heme-containing peroxidases from white rot basidiomycetes, in contrast
to most proteins of fungal origin, are poorly produced in industrial
filamentous fungal strains. Factors limiting peroxidase production are
believed to operate at the posttranslational level. In particular, insufficient availability of the prosthetic group which is required for
peroxidase biosynthesis has been proposed to be an important bottleneck.
In this work, we analyzed the role of two components of the secretion
pathway, the chaperones calnexin and binding protein (BiP), in the
production of a fungal peroxidase. Expression of the Phanerochaete
chrysosporium manganese peroxidase (MnP) in Aspergillus niger resulted
in an increase in the expression level of the clxA and bipA genes. In a
heme-supplemented medium, where MnP was shown to be overproduced to
higher levels, induction of clxA and bipA was also higher.
Overexpression of these two chaperones in an MnP-producing strain was
analyzed for its effect on MnP production. Whereas bipA overexpression
seriously reduced MnP production, overexpression of calnexin resulted in
a four- to fivefold increase in the extracellular MnP levels. However, when additional heme was provided in the culture medium, calnexin
overexpression had no synergistic effect on MnP production. The possible
function of these two chaperones in MnP maturation and production is
discussed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Heme-containing peroxidases from white rot basidiomycetes, in contrast
to most proteins of fungal origin, are poorly produced in industrial
filamentous fungal strains. Factors limiting peroxidase production are
believed to operate at the posttranslational level. In particular, insufficient availability of the prosthetic group which is required for
peroxidase biosynthesis has been proposed to be an important bottleneck.
In this work, we analyzed the role of two components of the secretion
pathway, the chaperones calnexin and binding protein (BiP), in the
production of a fungal peroxidase. Expression of the Phanerochaete
chrysosporium manganese peroxidase (MnP) in Aspergillus niger resulted
in an increase in the expression level of the clxA and bipA genes. In a
heme-supplemented medium, where MnP was shown to be overproduced to
higher levels, induction of clxA and bipA was also higher.
Overexpression of these two chaperones in an MnP-producing strain was
analyzed for its effect on MnP production. Whereas bipA overexpression
seriously reduced MnP production, overexpression of calnexin resulted in
a four- to fivefold increase in the extracellular MnP levels. However, when additional heme was provided in the culture medium, calnexin
overexpression had no synergistic effect on MnP production. The possible
function of these two chaperones in MnP maturation and production is
discussed.
to most proteins of fungal origin, are poorly produced in industrial
filamentous fungal strains. Factors limiting peroxidase production are
believed to operate at the posttranslational level. In particular, insufficient availability of the prosthetic group which is required for
peroxidase biosynthesis has been proposed to be an important bottleneck.
In this work, we analyzed the role of two components of the secretion
pathway, the chaperones calnexin and binding protein (BiP), in the
production of a fungal peroxidase. Expression of the Phanerochaete
chrysosporium manganese peroxidase (MnP) in Aspergillus niger resulted
in an increase in the expression level of the clxA and bipA genes. In a
heme-supplemented medium, where MnP was shown to be overproduced to
higher levels, induction of clxA and bipA was also higher.
Overexpression of these two chaperones in an MnP-producing strain was
analyzed for its effect on MnP production. Whereas bipA overexpression
seriously reduced MnP production, overexpression of calnexin resulted in
a four- to fivefold increase in the extracellular MnP levels. However, when additional heme was provided in the culture medium, calnexin
overexpression had no synergistic effect on MnP production. The possible
function of these two chaperones in MnP maturation and production is
discussed.
2001
4.
Conesa, A.; Punt, P.; van Luijk, N.; van den Hondel, C.
The secretion pathway in filamentous fungi: A biotechnological view Journal Article
In: FUNGAL GENETICS AND BIOLOGY, vol. 33, no. 3, pp. 155-171, 2001, ISSN: 1087-1845.
@article{ISI:000170506100001,
title = {The secretion pathway in filamentous fungi: A biotechnological view},
author = { A. Conesa and P. Punt and N. van Luijk and C. van den Hondel},
url = {http://dx.doi.org/10.1006/fgbe.2001.1276},
doi = {10.1006/fgbe.2001.1276},
issn = {1087-1845},
year = {2001},
date = {2001-08-01},
journal = {FUNGAL GENETICS AND BIOLOGY},
volume = {33},
number = {3},
pages = {155-171},
abstract = {The high capacity of the secretion machinery of filamentous fungi has
been widely exploited for the production of homologous and heterologous
proteins; however, our knowledge of the fungal secretion pathway is
still at an early stage. Most of the knowledge comes from models
developed in yeast and higher eukaryotes, which have served as reference
for the studies on fungal species. In this review we compile the data
accumulated in recent years on the molecular basis of fungal secretion, emphasizing the relevance of these data for the biotechnological use of
the fungal cell and indicating how this information has been applied in
attempts to create improved production strains. We also present recent
emerging approaches that promise to provide answers to fundamental
questions on the molecular genetics of the fungal secretory pathway. (C)
2001 Academic Press.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The high capacity of the secretion machinery of filamentous fungi has
been widely exploited for the production of homologous and heterologous
proteins; however, our knowledge of the fungal secretion pathway is
still at an early stage. Most of the knowledge comes from models
developed in yeast and higher eukaryotes, which have served as reference
for the studies on fungal species. In this review we compile the data
accumulated in recent years on the molecular basis of fungal secretion, emphasizing the relevance of these data for the biotechnological use of
the fungal cell and indicating how this information has been applied in
attempts to create improved production strains. We also present recent
emerging approaches that promise to provide answers to fundamental
questions on the molecular genetics of the fungal secretory pathway. (C)
2001 Academic Press.
been widely exploited for the production of homologous and heterologous
proteins; however, our knowledge of the fungal secretion pathway is
still at an early stage. Most of the knowledge comes from models
developed in yeast and higher eukaryotes, which have served as reference
for the studies on fungal species. In this review we compile the data
accumulated in recent years on the molecular basis of fungal secretion, emphasizing the relevance of these data for the biotechnological use of
the fungal cell and indicating how this information has been applied in
attempts to create improved production strains. We also present recent
emerging approaches that promise to provide answers to fundamental
questions on the molecular genetics of the fungal secretory pathway. (C)
2001 Academic Press.
3.
Conesa, A.; Weelink, G.; van den Hondel, C.; Punt, P.
C-terminal propeptide of the Caldariomyces fumago chloroperoxidase: an intramolecular chaperone? Journal Article
In: FEBS LETTERS, vol. 503, no. 2-3, pp. 117-120, 2001, ISSN: 0014-5793.
@article{ISI:000170641000001,
title = {C-terminal propeptide of the Caldariomyces fumago chloroperoxidase: an
intramolecular chaperone?},
author = { A. Conesa and G. Weelink and C. van den Hondel and P. Punt},
url = {http://dx.doi.org/10.1016/S0014-5793(01)02698-9},
doi = {10.1016/S0014-5793(01)02698-9},
issn = {0014-5793},
year = {2001},
date = {2001-08-01},
journal = {FEBS LETTERS},
volume = {503},
number = {2-3},
pages = {117-120},
abstract = {The Caldariomyces fumago chloroperoxidase (CPO) is synthesised as a
372-aa precursor which undergoes two proteolytic processing events.
removal of a 21-aa N-terminal signal peptide and of a 52-aa C-terminal
propeptide. The Aspergillus niger expression system developed for CPO
was used to get insight into the function of this C-terminal propeptide.
A. niger transformants expressing a CPO protein from which the
C-terminal propeptide was deleted failed in producing any extracellular
CPO activity, although the CPO polypeptide was synthesised. Expression
of the full-length gene in an A. niger strain lacking the KEX2-like
protease PclA also resulted in the production of CPO cross-reactive
material into the culture medium, but no CPO activity. Based on these
results, a function of the C-terminal propeptide in CPO maturation is
indicated. (C) 2001 Federation of European Biochemical Societies.
Published by Elsevier Science B.V. All rights reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The Caldariomyces fumago chloroperoxidase (CPO) is synthesised as a
372-aa precursor which undergoes two proteolytic processing events.
removal of a 21-aa N-terminal signal peptide and of a 52-aa C-terminal
propeptide. The Aspergillus niger expression system developed for CPO
was used to get insight into the function of this C-terminal propeptide.
A. niger transformants expressing a CPO protein from which the
C-terminal propeptide was deleted failed in producing any extracellular
CPO activity, although the CPO polypeptide was synthesised. Expression
of the full-length gene in an A. niger strain lacking the KEX2-like
protease PclA also resulted in the production of CPO cross-reactive
material into the culture medium, but no CPO activity. Based on these
results, a function of the C-terminal propeptide in CPO maturation is
indicated. (C) 2001 Federation of European Biochemical Societies.
Published by Elsevier Science B.V. All rights reserved.
372-aa precursor which undergoes two proteolytic processing events.
removal of a 21-aa N-terminal signal peptide and of a 52-aa C-terminal
propeptide. The Aspergillus niger expression system developed for CPO
was used to get insight into the function of this C-terminal propeptide.
A. niger transformants expressing a CPO protein from which the
C-terminal propeptide was deleted failed in producing any extracellular
CPO activity, although the CPO polypeptide was synthesised. Expression
of the full-length gene in an A. niger strain lacking the KEX2-like
protease PclA also resulted in the production of CPO cross-reactive
material into the culture medium, but no CPO activity. Based on these
results, a function of the C-terminal propeptide in CPO maturation is
indicated. (C) 2001 Federation of European Biochemical Societies.
Published by Elsevier Science B.V. All rights reserved.
2.
Conesa, A.; van de Velde, F.; van Rantwijk, F.; Sheldon, R.; van den Hondel, C.; Punt, P.
Expression of the Caldariomyces fumago chloroperoxidase in Aspergillus niger and characterization of the recombinant enzyme Journal Article
In: JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 276, no. 21, pp. 17635-17640, 2001, ISSN: 0021-9258.
@article{ISI:000168866500004,
title = {Expression of the Caldariomyces fumago chloroperoxidase in Aspergillus
niger and characterization of the recombinant enzyme},
author = { A. Conesa and F. van de Velde and F. van Rantwijk and R. Sheldon and C. van den Hondel and P. Punt},
url = {http://dx.doi.org/10.1074/jbc.M010571200},
doi = {10.1074/jbc.M010571200},
issn = {0021-9258},
year = {2001},
date = {2001-05-01},
journal = {JOURNAL OF BIOLOGICAL CHEMISTRY},
volume = {276},
number = {21},
pages = {17635-17640},
abstract = {The Caldariomyces fumago chloroperoxidase was successfully expressed in
Aspergillus niger. The recombinant enzyme was produced in the culture
medium as an active protein and could be purified by a three-step
purification procedure. The catalytic behavior of recombinant
chloroperoxidase (rCPO) was studied and compared with that of native
CPO. The specific chlorination activity (47 units/nmol) of rCPO and its
pH optimum (pH 2.75) were very similar to those of native CPO. rCPO
catalyzes the oxidation of various substrates in comparable yields and
selectivities to native CPO. Indole was oxidized to 2-oxindole with 99%
selectivity and thioanisole to the corresponding R-sulfoxide
(enantiomeric excess >98%). Incorporation of O-18 from labeled
(H2O2)-O-18 into the oxidized products was 100% in both cases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The Caldariomyces fumago chloroperoxidase was successfully expressed in
Aspergillus niger. The recombinant enzyme was produced in the culture
medium as an active protein and could be purified by a three-step
purification procedure. The catalytic behavior of recombinant
chloroperoxidase (rCPO) was studied and compared with that of native
CPO. The specific chlorination activity (47 units/nmol) of rCPO and its
pH optimum (pH 2.75) were very similar to those of native CPO. rCPO
catalyzes the oxidation of various substrates in comparable yields and
selectivities to native CPO. Indole was oxidized to 2-oxindole with 99%
selectivity and thioanisole to the corresponding R-sulfoxide
(enantiomeric excess >98%). Incorporation of O-18 from labeled
(H2O2)-O-18 into the oxidized products was 100% in both cases.
Aspergillus niger. The recombinant enzyme was produced in the culture
medium as an active protein and could be purified by a three-step
purification procedure. The catalytic behavior of recombinant
chloroperoxidase (rCPO) was studied and compared with that of native
CPO. The specific chlorination activity (47 units/nmol) of rCPO and its
pH optimum (pH 2.75) were very similar to those of native CPO. rCPO
catalyzes the oxidation of various substrates in comparable yields and
selectivities to native CPO. Indole was oxidized to 2-oxindole with 99%
selectivity and thioanisole to the corresponding R-sulfoxide
(enantiomeric excess >98%). Incorporation of O-18 from labeled
(H2O2)-O-18 into the oxidized products was 100% in both cases.
2000
1.
Conesa, A.; van den Hondel, C.; Punt, P.
Studies on the production of fungal peroxidases in Aspergillus niger Journal Article
In: APPLIED AND ENVIRONMENTAL MICROBIOLOGY, vol. 66, no. 7, pp. 3016-3023, 2000, ISSN: 0099-2240.
@article{ISI:000088057600044,
title = {Studies on the production of fungal peroxidases in Aspergillus niger},
author = { A. Conesa and C. van den Hondel and P. Punt},
url = {http://dx.doi.org/10.1128/AEM.66.7.3016-3023.2000},
doi = {10.1128/AEM.66.7.3016-3023.2000},
issn = {0099-2240},
year = {2000},
date = {2000-07-01},
journal = {APPLIED AND ENVIRONMENTAL MICROBIOLOGY},
volume = {66},
number = {7},
pages = {3016-3023},
abstract = {To get insight into the limiting factors existing for the efficient
production of fungal peroxidase in filamentous fungi, the expression of
the Phanerochaete chrysosporium lignin peroxidase H8 (lipA) and
manganese peroxidase (MnP) H4 (mnp1) genes in Aspergillus niger has been
studied. For this purpose, a protease-deficient A. niger strain and
different expression cassettes have been used. Northern blotting
experiments indicated high steady-state mRNA levels for the recombinant
genes. Manganese peroxidase was secreted into the culture medium as an
active protein. The recombinant protein showed specific activity and a
spectrum profile similar to those of the native enzyme, was correctly
processed at its N terminus, and had a slightly lower mobility on sodium
dodecyl sulfate-polyacrylamide gel electrophoresis, Recombinant MnP
production could be increased up to 100 mg/liter upon hemoglobin
supplementation of the culture medium. Lignin peroxidase was also
secreted into the extracellular medium, although the protein was not
active, presumably due to incorrect processing of the secreted enzyme.
Expression of the lipA and mnp1 genes fused to the A. niger glucoamylase
gene did not result in improved production yields.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
To get insight into the limiting factors existing for the efficient
production of fungal peroxidase in filamentous fungi, the expression of
the Phanerochaete chrysosporium lignin peroxidase H8 (lipA) and
manganese peroxidase (MnP) H4 (mnp1) genes in Aspergillus niger has been
studied. For this purpose, a protease-deficient A. niger strain and
different expression cassettes have been used. Northern blotting
experiments indicated high steady-state mRNA levels for the recombinant
genes. Manganese peroxidase was secreted into the culture medium as an
active protein. The recombinant protein showed specific activity and a
spectrum profile similar to those of the native enzyme, was correctly
processed at its N terminus, and had a slightly lower mobility on sodium
dodecyl sulfate-polyacrylamide gel electrophoresis, Recombinant MnP
production could be increased up to 100 mg/liter upon hemoglobin
supplementation of the culture medium. Lignin peroxidase was also
secreted into the extracellular medium, although the protein was not
active, presumably due to incorrect processing of the secreted enzyme.
Expression of the lipA and mnp1 genes fused to the A. niger glucoamylase
gene did not result in improved production yields.
production of fungal peroxidase in filamentous fungi, the expression of
the Phanerochaete chrysosporium lignin peroxidase H8 (lipA) and
manganese peroxidase (MnP) H4 (mnp1) genes in Aspergillus niger has been
studied. For this purpose, a protease-deficient A. niger strain and
different expression cassettes have been used. Northern blotting
experiments indicated high steady-state mRNA levels for the recombinant
genes. Manganese peroxidase was secreted into the culture medium as an
active protein. The recombinant protein showed specific activity and a
spectrum profile similar to those of the native enzyme, was correctly
processed at its N terminus, and had a slightly lower mobility on sodium
dodecyl sulfate-polyacrylamide gel electrophoresis, Recombinant MnP
production could be increased up to 100 mg/liter upon hemoglobin
supplementation of the culture medium. Lignin peroxidase was also
secreted into the extracellular medium, although the protein was not
active, presumably due to incorrect processing of the secreted enzyme.
Expression of the lipA and mnp1 genes fused to the A. niger glucoamylase
gene did not result in improved production yields.
