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}
}
132.
Arzalluz-Luque, Ángeles; Cabrera, Jose Luis; Skottman, Heli; Benguria, Alberto; Bolinches-Amorós, Arantxa; Cuenca, Nicolás; Lupo, Vincenzo; Dopazo, Ana; Tarazona, Sonia; Delás, Bárbara; Carballo, Miguel; Pascual, Beatriz; Hernan, Imma; Erceg, Slaven; Lukovic, Dunja
Mutant PRPF8 Causes Widespread Splicing Changes in Spliceosome Components in Retinitis Pigmentosa Patient iPSC-Derived RPE Cells Journal Article
In: Front Neurosci, vol. 15, pp. 636969, 2021, ISSN: 1662-4548.
@article{pmid33994920,
title = {Mutant PRPF8 Causes Widespread Splicing Changes in Spliceosome Components in Retinitis Pigmentosa Patient iPSC-Derived RPE Cells},
author = {Ángeles Arzalluz-Luque and Jose Luis Cabrera and Heli Skottman and Alberto Benguria and Arantxa Bolinches-Amorós and Nicolás Cuenca and Vincenzo Lupo and Ana Dopazo and Sonia Tarazona and Bárbara Delás and Miguel Carballo and Beatriz Pascual and Imma Hernan and Slaven Erceg and Dunja Lukovic},
doi = {10.3389/fnins.2021.636969},
issn = {1662-4548},
year = {2021},
date = {2021-01-01},
journal = {Front Neurosci},
volume = {15},
pages = {636969},
abstract = {Retinitis pigmentosa (RP) is a rare, progressive disease that affects photoreceptors and retinal pigment epithelial (RPE) cells with blindness as a final outcome. Despite high medical and social impact, there is currently no therapeutic options to slow down the progression of or cure the disease. The development of effective therapies was largely hindered by high genetic heterogeneity, inaccessible disease tissue, and unfaithful model organisms. The fact that components of ubiquitously expressed splicing factors lead to the retina-specific disease is an additional intriguing question. Herein, we sought to correlate the retinal cell-type-specific disease phenotype with the splicing profile shown by a patient with autosomal recessive RP, caused by a mutation in pre-mRNA splicing factor 8 (PRPF8). In order to get insight into the role of PRPF8 in homeostasis and disease, we capitalize on the ability to generate patient-specific RPE cells and reveal differentially expressed genes unique to RPE cells. We found that spliceosomal complex and ribosomal functions are crucial in determining cell-type specificity through differential expression and alternative splicing (AS) and that PRPF8 mutation causes global changes in splice site selection and exon inclusion that particularly affect genes involved in these cellular functions. This finding corroborates the hypothesis that retinal tissue identity is conferred by a specific splicing program and identifies retinal AS events as a framework toward the design of novel therapeutic opportunities.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Retinitis pigmentosa (RP) is a rare, progressive disease that affects photoreceptors and retinal pigment epithelial (RPE) cells with blindness as a final outcome. Despite high medical and social impact, there is currently no therapeutic options to slow down the progression of or cure the disease. The development of effective therapies was largely hindered by high genetic heterogeneity, inaccessible disease tissue, and unfaithful model organisms. The fact that components of ubiquitously expressed splicing factors lead to the retina-specific disease is an additional intriguing question. Herein, we sought to correlate the retinal cell-type-specific disease phenotype with the splicing profile shown by a patient with autosomal recessive RP, caused by a mutation in pre-mRNA splicing factor 8 (PRPF8). In order to get insight into the role of PRPF8 in homeostasis and disease, we capitalize on the ability to generate patient-specific RPE cells and reveal differentially expressed genes unique to RPE cells. We found that spliceosomal complex and ribosomal functions are crucial in determining cell-type specificity through differential expression and alternative splicing (AS) and that PRPF8 mutation causes global changes in splice site selection and exon inclusion that particularly affect genes involved in these cellular functions. This finding corroborates the hypothesis that retinal tissue identity is conferred by a specific splicing program and identifies retinal AS events as a framework toward the design of novel therapeutic opportunities.
131.
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.
130.
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.
129.
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.
128.
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}
}
127.
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}
}
126.
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}
}
125.
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}
}
124.
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}
}
123.
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.
122.
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.
121.
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}
}
120.
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}
}
119.
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.
118.
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.
117.
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.
116.
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}
}
115.
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.