2021 |
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| 144. | van der Planell N Lagani V, Sebastian-Leon Kloet Ewing Karathanasis Urdangarin Arozarena Jagodic Tsamardinos Tarazona Conesa Tegner Gomez-Cabrero P F E N A I M I S A J D STATegra: Multi-Omics Data Integration - A Conceptual Scheme With a Bioinformatics Pipeline (Journal Article) Frontiers in Genetics, 12 , pp. 620453, 2021. @article{N2021, title = {STATegra: Multi-Omics Data Integration - A Conceptual Scheme With a Bioinformatics Pipeline}, author = {Planell N, Lagani V, Sebastian-Leon P, van der Kloet F, Ewing E, Karathanasis N, Urdangarin A, Arozarena I, Jagodic M, Tsamardinos I, Tarazona S, Conesa A, Tegner J, Gomez-Cabrero D}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970106/pdf/fgene-12-620453.pdf}, doi = {0.3389/fgene.2021.620453}, year = {2021}, date = {2021-03-04}, journal = {Frontiers in Genetics}, 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. |
| 143. | Arzalluz-Luque, Angeles; Salguero, Pedro; Tarazona, Sonia; Conesa, Ana Acorde: unraveling functionally-interpretable networks of isoform co-usage from single cell data (Journal Article) bioRxiv, 2021. (BibTeX) @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} } |
| 142. | 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) bioRxiv, 2021. (BibTeX) @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} } |
| 141. | ~n, Jes{'u}s Rodr{'i}guez-Ba; Pachón, Jerónimo; `a, Jordi Carratal; Ryan, Pablo; 'i, Inmaculada Jarr; 'i, Mar; Arribas, José Ramón; Berenguer, Juan; ~n, Esther Aznar Mu; Divasson, Pedro Gil; others, Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19) (Journal Article) Clinical Microbiology and Infection, 27 (2), pp. 244–252, 2021. (BibTeX) @article{rodriguez2021treatment, title = {Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)}, author = {Jes{'u}s Rodr{'i}guez-Ba{~n}o and Jerónimo Pachón and Jordi Carratal{`a} and Pablo Ryan and Inmaculada Jarr{'i}n and Mar{'i}a Yllescas and José Ramón Arribas and Juan Berenguer and Esther Aznar Mu{~n}oz and Pedro Gil Divasson and others}, year = {2021}, date = {2021-01-01}, journal = {Clinical Microbiology and Infection}, volume = {27}, number = {2}, pages = {244--252}, publisher = {Elsevier}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
| 140. | 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) bioRxiv, 2021. (BibTeX) @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} } |
| 139. | Rubio, Teresa; Felipo, Vicente; Tarazona, Sonia; Pastorelli, Roberta; 'i, Desamparados Escudero-Garc; 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) Scientific reports, 11 (1), pp. 1–14, 2021. (BibTeX) @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} } |
| 138. | Balzano-Nogueira, Leandro; Ramirez, Ricardo; Zamkovaya, Tatyana; Dailey, Jordan; Ardissone, Alexandria N; Chamala, Srikar; 'i, Joan Serrano-Qu; 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) Genome biology, 22 (1), pp. 1–27, 2021. (BibTeX) @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} } |
| 137. | 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) Cell Biology and Toxicology, 37 (1), pp. 129–149, 2021. (BibTeX) @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} } |
| 136. | 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) The ISME Journal, 15 (1), pp. 228–244, 2021. (BibTeX) @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 |
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| 135. | Tarazona S Balzano-Nogueira L, Gómez-Cabrero Schmidt Imhof Hankemeier Tegnér Westerhuis JA Conesa D A A T J A Harmonization of quality metrics and power calculation in multi-omic studies (Journal Article) Nature Communications, 11 (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. |
| 134. | 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) Statistical Methods in Medical Research, 0 (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. |
| 133. | 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) Scientific data, 7 (1), pp. 69-69, 2020, ISSN: 2052-4463, (32109230[pmid]). @article{Nuño-Cabanes2020, title = {A multi-omics dataset of heat-shock response in the yeast RNA binding protein Mip6}, author = {Nuño, Carme and Ugidos, Manuel and Tarazona, Sonia and Martín-Expósito, Manuel and Ferrer, Alberto and Rodríguez-Navarro, Susana and Conesa, Ana}, 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. |
| 132. | 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) Scientific data, 7 (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. |
| 131. | McIntyre, Lauren M; Huertas, Francisco; Moskalenko, Olexander; Llansola, Marta; Felipo, Vicente; Morse, Alison M; Conesa, Ana GAIT-GM: Galaxy tools for modeling metabolite changes as a function of gene expression (Journal Article) bioRxiv, 2020. (BibTeX) @article{mcintyre2020gait, title = {GAIT-GM: Galaxy tools for modeling metabolite changes as a function of gene expression}, author = {Lauren M McIntyre and Francisco Huertas and Olexander Moskalenko and Marta Llansola and Vicente Felipo and Alison M Morse and Ana Conesa}, year = {2020}, date = {2020-01-01}, journal = {bioRxiv}, publisher = {Cold Spring Harbor Laboratory}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
| 130. | 'i, Salvador Casan; Pereira, Cecile; Conesa, Ana Padhoc: a computational pipeline for pathway reconstruction on the fly (Journal Article) Bioinformatics, 36 (Supplement_2), pp. i795–i803, 2020. (BibTeX) @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} } |
| 129. | Ylla, Guillem; Liu, Tianyuan; Conesa, Ana MirCure: a tool for quality control, filter and curation of microRNAs of animals and plants (Journal Article) Bioinformatics, 36 (Supplement_2), pp. i618–i624, 2020. (BibTeX) @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} } |
| 128. | 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) BMC plant biology, 20 (1), pp. 1–17, 2020. (BibTeX) @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} } |
| 127. | 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) Genes, 11 (12), pp. 1447, 2020. (BibTeX) @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} } |
| 126. | 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) Scientific reports, 10 (1), pp. 1–15, 2020. (BibTeX) @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} } |
| 125. | de la Fuente, Lorena; Arzalluz-Luque, Ángeles; Tardáguila, Manuel; Risco, Héctor Del; 'i, Cristina Mart; 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) Genome biology, 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 |
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| 124. | 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) PLOS Computational Biology, 15 (11), pp. e1006555, 2019, ISSN: 1553-7358. @article{Jansen2019, 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 = {Leslie, Christina S.}, 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} } |
| 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) Journal of bacteriology, 201 (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) PLOS Computational Biology, 15 (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) 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) ACS Chemical Neuroscience, 10 (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 Paul, Veronica Saint; 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) Scientific data, 6 (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 Turpin-Sevilla, María Carmen; 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) Histopathology, 75 (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) Scientific data, 6 (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) PLoS Biology, 17 (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) Database, 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 |
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| 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) npj Microgravity, 4 (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 Elucidating the Role of Chromatin State and Transcription Factors on the Regulation of the Yeast Metabolic Cycle: A Multi-Omic Integrative Approach (Journal Article) Frontiers in Genetics, 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) Clinical Epigenetics, 10 (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) Nature communications, 9 (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) Molecular Reproduction and Development, 0 (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 Elucidating the Role of Chromatin State and Transcription Factors on the Regulation of the Yeast Metabolic Cycle: A Multi-Omic Integrative Approach (Journal Article) Frontiers in Genetics, 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) Biomaterials, 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) Data in Brief, 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) G3: Genes, Genomes, Genetics, 8 (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) Genome Biology, 19 (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) Aquatic Toxicology, 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) Comprehensive Analytical Chemistry, 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 ; Pappas Jr, Georgios J; Conesa, Ana PaintOmics 3: a web resource for the pathway analysis and visualization of multi-omics data (Journal Article) 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, Pamela R; Foster, Jamie S Comparative Metagenomics Provides Insight Into the Ecosystem Functioning of the Shark Bay Stromatolites, Western Australia (Journal Article) Frontiers in Microbiology, 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) Genome Biology and Evolution, 10 (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) Bioinformatics, 34 (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, Franklin B; 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) Epigenetics & Chromatin, 11 (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 SQANTI: extensive characterization of long-read transcript sequences for quality control in full-length transcriptome identification and quantification (Journal Article) 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) Bioinformatics, 34 (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) 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 |
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| 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) FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 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. |
| 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 GENOME RESEARCH, 27 (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. |
| 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) 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, Ramon J; del Navarro, Pilar M; Rubio-Munoz, P; Ahijado-Guzman, P; Gonzalez, C M Certolizumab Pegol Effectiveness and Retention Rate in Psoriatic Arthritis. Real Life Data (Journal Article) ARTHRITIS & RHEUMATOLOGY, 69 (10), 2017, ISSN: 2326-5191. (BibTeX) @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) CELL SYSTEMS, 5 (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. |
| 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) PLOS COMPUTATIONAL BIOLOGY, 13 (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. |
| 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) CELL SYSTEMS, 4 (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. |
| 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) REPRODUCTIVE SCIENCES, 24 (1), pp. 162A, 2017, ISSN: 1933-7191, (64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Orlando, FL, MAR 15-18, 2017). (BibTeX) @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, Lucia P; Gonzalez-Rodriguez, E; Aguado-Santacruz, Armando G; 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) COMPUTATIONAL BIOLOGY AND CHEMISTRY, 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. |
2016 |
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| 85. | Blaustein, R; Meyer, J; Conesa, A; Lorca, G; Teplitski, M Impacts of abundance of Candidatus Liberibacter on the citrus phyto-microbiome (Journal Article) PHYTOPATHOLOGY, 106 (12, S), pp. 25-26, 2016, ISSN: 0031-949X, (Annual Meeting of the American-Phytopathological-Society (APS), Tampa, FL, JUL 30-AUG 03, 2016). (BibTeX) @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, Del S; Delogne, C; Devilee, P; Meglio, Di A; 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, Redon J; 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) GENOME MEDICINE, 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) BMC BIOINFORMATICS, 17 (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. |
| 82. | Panis, De D N; Padro, J; Furio-Tari, P; Tarazona, S; Carmona, Milla P S; Soto, I M; Dopazo, H; Conesa, A; Hasson, E Transcriptome modulation during host shift is driven by secondary metabolites in desert Drosophila (Journal Article) MOLECULAR ECOLOGY, 25 (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. |
| 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) GENOME BIOLOGY, 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) NUCLEIC ACIDS RESEARCH, 44 (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. |
| 79. | Auffray, C; Balling, R; Barroso, I; Bencze, L; Benson, M; Bergeron, J; Bernal-Delgado, E; Blomberg, N; Bock, C; Conesa, A; Signore, Del S; Delogne, C; Devilee, P; Meglio, Di A; 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, Redon J; 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) GENOME MEDICINE, 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. |
| 78. | van der Kloet, F M; Sebastian-Leon, P; Conesa, A; Smilde, A K; Westerhuis, J A Separating common from distinctive variation (Journal Article) BMC BIOINFORMATICS, 17 (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. |
| 77. | Okonechnikov, K; Conesa, A; Garcia-Alcalde, F Qualimap 2: advanced multi-sample quality control for high-throughput sequencing data (Journal Article) BIOINFORMATICS, 32 (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. |
| 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) GENOME BIOLOGY, 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. |
2015 |
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| 75. | Tarazona, S; Furio-Tari, P; Turra, D; Pietro, Di A; Nueda, Jose M; Ferrer, A; Conesa, A Data quality aware analysis of differential expression in RNA-seq with NOISeq R/Bioc package (Journal Article) NUCLEIC ACIDS RESEARCH, 43 (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. |
| 74. | Conesa-Zamora, P; Garcia-Solano, J; del Turpin, Carmen 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) CLINICAL EPIGENETICS, 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. |
| 73. | Morin-Adeline, V; Mueller, K; Conesa, A; Slapeta, J VETERINARY PARASITOLOGY, 212 (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. |
| 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) BMC GENOMICS, 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. |
| 71. | de la Fuente, L; Conesa, A; Lloret, A; Badenes, Luisa M; Rios, G Genome-wide changes in histone H3 lysine 27 trimethylation associated with bud dormancy release in peach (Journal Article) TREE GENETICS & GENOMES, 11 (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. |
| 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, Font J; Castel, V Two independent epigenetic biomarkers predict survival in neuroblastoma (Journal Article) CLINICAL EPIGENETICS, 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. |
2014 |
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| 69. | Morin-Adeline, V; Lomas, R; O'Meally, D; Stack, C; Conesa, A; Slapeta, J BMC GENOMICS, 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. |
| 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) BMC SYSTEMS BIOLOGY, 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. |
| 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) NATURE BIOTECHNOLOGY, 32 (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. |
| 66. | Nueda, M J; Tarazona, S; Conesa, A Next maSigPro: updating maSigPro bioconductor package for RNA-seq time series (Journal Article) BIOINFORMATICS, 30 (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. |
| 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) NATURE COMMUNICATIONS, 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. |
| 64. | Sevilla, Turpin M; 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) EUROPEAN JOURNAL OF CANCER, 50 (5), pp. S219, 2014, ISSN: 0959-8049. (BibTeX) @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, Bressac-de B; 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, Van A; Vidakovic, M; Widschwendter, M Relationship between genome and epigenome - challenges and requirements for future research (Journal Article) BMC GENOMICS, 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. |
| 62. | Larriba, E; Jaime, M D L A; Carbonell-Caballero, J; Conesa, A; Dopazo, J; Nislow, C; Martin-Nieto, J; Lopez-Llorca, Vicente L Sequencing and functional analysis of the genome of a nematode egg-parasitic fungus, Pochonia chlamydosporia (Journal Article) FUNGAL GENETICS AND BIOLOGY, 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. |
| 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) ANNALS OF APPLIED BIOLOGY, 164 (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) BMC SYSTEMS BIOLOGY, 8 (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. |
| 59. | Conesa, A; Mortazavi, A The common ground of genomics and systems biology (Journal Article) BMC SYSTEMS BIOLOGY, 8 (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. |
| 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) BMC SYSTEMS BIOLOGY, 8 (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. |
| 57. | de Diego, Hernandez R; 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) BMC SYSTEMS BIOLOGY, 8 (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. |
| 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) LABORATORY INVESTIGATION, 94 (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). (BibTeX) @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) MODERN PATHOLOGY, 27 (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). (BibTeX) @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 |
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| 54. | Galan, A; Diaz-Gimeno, P; Poo, Eugenia M; 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) PLOS ONE, 8 (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. |
| 53. | Conesa-Zamora, P; Garcia-Solano, J; Garcia-Garcia, F; del Turpin, Carmen M; Trujillo-Santos, J; Torres-Moreno, D; Oviedo-Ramirez, I; Carbonell-Munoz, R; Munoz-Delgado, E; Rodriguez-Braun, E; Conesa, A; Perez-Guillermo, M Expression profiling shows differential molecular pathways and provides potential new diagnostic biomarkers for colorectal serrated adenocarcinoma (Journal Article) INTERNATIONAL JOURNAL OF CANCER, 132 (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. |
2012 |
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| 52. | Yanez, Y; Grau, E; Canete, A; Conesa, A; Neira, Gonzalez A; Castel, V METHYLATION STATUS IN NEUROBLASTOMA AND ITS PROGNOSTIC VALUE (Journal Article) PEDIATRIC BLOOD & CANCER, 59 (6, SI), pp. 1053-1054, 2012, ISSN: 1545-5009. (BibTeX) @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 MOLECULAR PLANT PATHOLOGY, 13 (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. |
| 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) BIOINFORMATICS, 28 (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. |
| 49. | Fernandez, P; Soria, M; Blesa, D; DiRienzo, J; Moschen, S; Rivarola, M; Clavijo, Jose B; Gonzalez, S; Peluffo, L; Principi, D; Dosio, G; Aguirrezabal, L; Garcia-Garcia, F; Conesa, A; Hopp, E; Dopazo, J; Heinz, Amelia R; Paniego, N Development, Characterization and Experimental Validation of a Cultivated Sunflower (Helianthus annuus L.) Gene Expression Oligonucleotide Microarray (Journal Article) PLOS ONE, 7 (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. |
| 48. | Agusti, J; Gimeno, J; Merelo, P; Serrano, R; Cercos, M; Conesa, A; Talon, M; Tadeo, F R JOURNAL OF EXPERIMENTAL BOTANY, 63 (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. |
| 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) BIOSTATISTICS, 13 (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. |
| 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) MYCOSES, 55 (4, SI), pp. 135-136, 2012, ISSN: 0933-7407. (BibTeX) @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, Vicente L; 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) BMC GENOMICS, 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. |
| 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) BIOTECHNOLOGY LETTERS, 34 (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. |
| 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) PLOS ONE, 7 (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. |
| 42. | Carcel-Trullols, J; Aguilar-Gallardo, C; Garcia-Alcalde, F; Pardo-Cea, Angel M; 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) SPRINGERPLUS, 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. |
| 41. | Leida, C; Conesa, A; Llacer, G; Badenes, Luisa M; Rios, G Histone modifications and expression of DAM6 gene in peach are modulated during bud dormancy release in a cultivar-dependent manner (Journal Article) NEW PHYTOLOGIST, 193 (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. |
| 40. | Tarazona, S; Prado-Lopez, S; Dopazo, J; Ferrer, A; Conesa, A Variable selection for multifactorial genomic data (Journal Article) CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS, 110 (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. |
2011 |
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| 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 HUMAN MOLECULAR GENETICS, 20 (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. |
| 38. | Tarazona, S; Garcia-Alcalde, F; Dopazo, J; Ferrer, A; Conesa, A Differential expression in RNA-seq: A matter of depth (Journal Article) GENOME RESEARCH, 21 (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. |
| 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) BMC PLANT BIOLOGY, 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. |
| 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) BMC GENOMICS, 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. |
| 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) BIOINFORMATICS, 27 (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. |
| 34. | Garrido-Gomez, T; Dominguez, F; Lopez, Antonio J; Camafeita, E; Quinonero, A; Martinez-Conejero, Antonio J; Pellicer, A; Conesa, A; Simon, C Modeling Human Endometrial Decidualization from the Interaction between Proteome and Secretome (Journal Article) JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 96 (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) |
| 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) BIOINFORMATICS, 27 (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. |
2010 |
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| 32. | Conesa, A; Prats-Montalban, J M; Tarazona, S; Nueda, Jose M; Ferrer, A A multiway approach to data integration in systems biology based on Tucker3 and N-PLS (Journal Article) CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS, 104 (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. |
| 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) NUCLEIC ACIDS RESEARCH, 38 (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. |
| 30. | Nueda, Jose M; Carbonell, J; Medina, I; Dopazo, J; Conesa, A Serial Expression Analysis: a web tool for the analysis of serial gene expression data (Journal Article) NUCLEIC ACIDS RESEARCH, 38 (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. |
| 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) PLOS GENETICS, 6 (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. |
| 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, Enrique J; Moreno, R; Dopazo, J; Burks, D J; Stojkovic, M Hypoxia Promotes Efficient Differentiation of Human Embryonic Stem Cells to Functional Endothelium (Journal Article) STEM CELLS, 28 (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 |
| 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) NUCLEIC ACIDS RESEARCH, 38 (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). |
2009 |
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| 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 Membrane transporters and carbon metabolism implicated in chloride homeostasis differentiate salt stress responses in tolerant and sensitive Citrus rootstocks (Journal Article) FUNCTIONAL & INTEGRATIVE GENOMICS, 9 (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. |
| 25. | Nueda, Jose M; Sebastian, P; Tarazona, S; Garcia-Garcia, F; Dopazo, J; Ferrer, A; Conesa, A Functional assessment of time course microarray data (Journal Article) BMC BIOINFORMATICS, 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. |
2008 |
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| 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) GENOMICS, 92 (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. |
| 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) GASTROENTEROLOGY, 135 (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. |
| 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 FOOD AND CHEMICAL TOXICOLOGY, 46 (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. |
| 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) NUCLEIC ACIDS RESEARCH, 36 (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. |
| 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) NUCLEIC ACIDS RESEARCH, 36 (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. |
| 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) BMC GENOMICS, 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. |
| 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) NUCLEIC ACIDS RESEARCH, 36 (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. |
| 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) MOLECULAR VISION, 14 (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. |
2007 |
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| 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) EUKARYOTIC CELL, 6 (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. |
| 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) VIROLOGY, 367 (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. |
| 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) BIOINFORMATICS, 23 (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. |
| 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) BMC GENOMICS, 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. |
2006 |
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| 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 Development of the GENIPOL European flounder (Platichthys flesus) microarray and determination of temporal transcriptional responses to cadmium at low dose. (Journal Article) ENVIRONMENTAL SCIENCE & TECHNOLOGY, 40 (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. |
| 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) BIOINFORMATICS, 22 (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. |
2005 |
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| 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) BIOINFORMATICS, 21 (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. |
| 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) PLANT MOLECULAR BIOLOGY, 57 (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. |
2003 |
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| 8. | Yi, X; Conesa, A; Punt, P; Hager, L Examining the role of glutamic acid 183 in chloroperoxidase catalysis (Journal Article) JOURNAL OF BIOLOGICAL CHEMISTRY, 278 (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. |
2002 |
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| 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) TRENDS IN BIOTECHNOLOGY, 20 (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. |
| 6. | Conesa, A; Punt, P; van den Hondel, C Fungal peroxidases: molecular aspects and applications (Journal Article) JOURNAL OF BIOTECHNOLOGY, 93 (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. |
| 5. | Conesa, A; Jeenes, D; Archer, D; van den Hondel, C; Punt, P Calnexin overexpression increases manganese peroxidase production in Aspergillus niger (Journal Article) APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 68 (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. |
2001 |
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| 4. | Conesa, A; Punt, P; van Luijk, N; van den Hondel, C The secretion pathway in filamentous fungi: A biotechnological view (Journal Article) FUNGAL GENETICS AND BIOLOGY, 33 (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. |
| 3. | Conesa, A; Weelink, G; van den Hondel, C; Punt, P C-terminal propeptide of the Caldariomyces fumago chloroperoxidase: an intramolecular chaperone? (Journal Article) FEBS LETTERS, 503 (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. |
| 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) JOURNAL OF BIOLOGICAL CHEMISTRY, 276 (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. |
2000 |
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| 1. | Conesa, A; van den Hondel, C; Punt, P Studies on the production of fungal peroxidases in Aspergillus niger (Journal Article) APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 66 (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. |
Publications
2021 |
|
| 144. | STATegra: Multi-Omics Data Integration - A Conceptual Scheme With a Bioinformatics Pipeline (Journal Article) Frontiers in Genetics, 12 , pp. 620453, 2021. |
| 143. | Acorde: unraveling functionally-interpretable networks of isoform co-usage from single cell data (Journal Article) bioRxiv, 2021. |
| 142. | Ozone sensitivity of diverse maize genotypes is associated with differences in gene regulation, not gene content (Journal Article) bioRxiv, 2021. |
| 141. | Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19) (Journal Article) Clinical Microbiology and Infection, 27 (2), pp. 244–252, 2021. |
| 140. | Circadian Transcriptomic and Epigenomic Remodeling in Response to Lipid Overload and Human Obesity (Journal Article) bioRxiv, 2021. |
| 139. | Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients (Journal Article) Scientific reports, 11 (1), pp. 1–14, 2021. |
| 138. | 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) Genome biology, 22 (1), pp. 1–27, 2021. |
| 137. | A multi-omic study for uncovering molecular mechanisms associated with hyperammonemia-induced cerebellar function impairment in rats (Journal Article) Cell Biology and Toxicology, 37 (1), pp. 129–149, 2021. |
| 136. | A network approach to elucidate and prioritize microbial dark matter in microbial communities (Journal Article) The ISME Journal, 15 (1), pp. 228–244, 2021. |
2020 |
|
| 135. | Harmonization of quality metrics and power calculation in multi-omic studies (Journal Article) Nature Communications, 11 (1), pp. 3092, 2020. |
| 134. | MultiBaC: A strategy to remove batch effects between different omic data types (Journal Article) Statistical Methods in Medical Research, 0 (0), pp. 1-14, 2020, (PMID: 32131696). |
| 133. | A multi-omics dataset of heat-shock response in the yeast RNA binding protein Mip6 (Journal Article) Scientific data, 7 (1), pp. 69-69, 2020, ISSN: 2052-4463, (32109230[pmid]). |
| 132. | A multi-omics dataset of heat-shock response in the yeast RNA binding protein Mip6 (Journal Article) Scientific data, 7 (1), pp. 69-69, 2020, ISSN: 2052-4463, (32109230[pmid]). |
| 131. | GAIT-GM: Galaxy tools for modeling metabolite changes as a function of gene expression (Journal Article) bioRxiv, 2020. |
| 130. | Padhoc: a computational pipeline for pathway reconstruction on the fly (Journal Article) Bioinformatics, 36 (Supplement_2), pp. i795–i803, 2020. |
| 129. | MirCure: a tool for quality control, filter and curation of microRNAs of animals and plants (Journal Article) Bioinformatics, 36 (Supplement_2), pp. i618–i624, 2020. |
| 128. | Sequencing and analysis of gerbera daisy leaf transcriptomes reveal disease resistance and susceptibility genes differentially expressed and associated with powdery mildew resistance (Journal Article) BMC plant biology, 20 (1), pp. 1–17, 2020. |
| 127. | Transcriptional differences for COVID-19 Disease Map genes between males and females indicate a different basal immunophenotype relevant to the disease (Journal Article) Genes, 11 (12), pp. 1447, 2020. |
| 126. | Assessment of unconventional antimicrobial compounds for the control of ‘Candidatus liberibacter asiaticus’, the causative agent of citrus greening disease (Journal Article) Scientific reports, 10 (1), pp. 1–15, 2020. |
| 125. | tappAS: a comprehensive computational framework for the analysis of the functional impact of differential splicing (Journal Article) Genome biology, 21 , pp. 1–32, 2020. |
2019 |
|
| 124. | Building gene regulatory networks from scATAC-seq and scRNA-seq using Linked Self Organizing Maps (Journal Article) PLOS Computational Biology, 15 (11), pp. e1006555, 2019, ISSN: 1553-7358. |
| 123. | Differential Modulation of Quorum Sensing Signaling through QslA in Pseudomonas aeruginosa Strains PAO1 and PA14 (Journal Article) Journal of bacteriology, 201 (21), 2019, ISSN: 10985530. |
| 122. | Building gene regulatory networks from scATAC-seq and scRNA-seq using Linked Self Organizing Maps (Journal Article) PLOS Computational Biology, 15 (11), pp. e1006555, 2019, ISSN: 1553-7358. |
| 121. | Mip6 binds directly to the Mex67 UBA domain to maintain low levels of Msn2/4 stress‐dependent mRNAs (Journal Article) EMBO reports, 2019, ISSN: 1469-221X. |
| 120. | A Multiomics Study to Unravel the Effects of Developmental Exposure to Endosulfan in Rats: Molecular Explanation for Sex-Dependent Effects (Journal Article) ACS Chemical Neuroscience, 10 (10), pp. 4264–4279, 2019, ISSN: 19487193. |
| 119. | STATegra, a comprehensive multi-omics dataset of B-cell differentiation in mouse (Journal Article) Scientific data, 6 (1), pp. 256, 2019, ISSN: 20524463. |
| 118. | Differences in gene expression profiling and biomarkers between histological colorectal carcinoma subsets from the serrated pathway (Journal Article) Histopathology, 75 (4), pp. 496–507, 2019, ISSN: 13652559. |
| 117. | Making multi-omics data accessible to researchers (Journal Article) Scientific data, 6 (1), pp. 251, 2019, ISSN: 20524463. |
| 116. | Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation (Journal Article) PLoS Biology, 17 (4), 2019, ISSN: 15457885. |
| 115. | Large expert-curated database for benchmarking document similarity detection in biomedical literature search (Journal Article) Database, 2019 , 2019, ISSN: 1758-0463, (baz085). |
2018 |
|
| 114. | Transcriptional profiling of the mutualistic bacterium Vibrio fischeri and an hfq mutant under modeled microgravity (Journal Article) npj Microgravity, 4 (1), pp. 25, 2018. |
| 113. | Elucidating the Role of Chromatin State and Transcription Factors on the Regulation of the Yeast Metabolic Cycle: A Multi-Omic Integrative Approach (Journal Article) Frontiers in Genetics, 9 , pp. 578, 2018, ISSN: 1664-8021. |
| 112. | Two histologically colorectal carcinomas subsets from the serrated pathway show different methylome signatures and diagnostic biomarkers (Journal Article) Clinical Epigenetics, 10 (1), pp. 141, 2018, ISSN: 1868-7083. |
| 111. | Overexpression of the vascular brassinosteroid receptor BRL3 confers drought resistance without penalizing plant growth (Journal Article) Nature communications, 9 (1), pp. 4680, 2018. |
| 110. | Changes in the uterine metabolome of the cow during the first seven days after estrus (Journal Article) Molecular Reproduction and Development, 0 (ja), 2018. |
| 109. | Elucidating the Role of Chromatin State and Transcription Factors on the Regulation of the Yeast Metabolic Cycle: A Multi-Omic Integrative Approach (Journal Article) Frontiers in Genetics, 9 , 2018, ISSN: 1664-8021. |
| 108. | Tumor microenvironment-targeted poly-L-glutamic acid-based combination conjugate for enhanced triple negative breast cancer treatment (Journal Article) Biomaterials, 186 , pp. 8 - 21, 2018, ISSN: 0142-9612. |
| 107. | Gene expression profile and molecular pathway datasets resulting from benzo(a)pyrene exposure in the liver and testis of adult tilapia (Journal Article) Data in Brief, 20 , pp. 1500 - 1509, 2018, ISSN: 2352-3409. |
| 106. | Event Analysis: Using Transcript Events To Improve Estimates of Abundance in RNA-seq Data (Journal Article) G3: Genes, Genomes, Genetics, 8 (9), pp. 2923–2940, 2018. |
| 105. | Single-cell RNAseq for the study of isoforms---how is that possible? (Journal Article) Genome Biology, 19 (1), pp. 110, 2018, ISSN: 1474-760X. |
| 104. | Transcriptome analysis reveals novel insights into the response of low-dose benzo(a)pyrene exposure in male tilapia (Journal Article) Aquatic Toxicology, 201 , pp. 162 - 173, 2018, ISSN: 0166-445X. |
| 103. | Multiomics Data Integration in Time Series Experiments (Journal Article) Comprehensive Analytical Chemistry, 8 , pp. 505-532, 2018. |
| 102. | PaintOmics 3: a web resource for the pathway analysis and visualization of multi-omics data (Journal Article) Nucleic Acids Research, pp. gky466, 2018. |
| 101. | Comparative Metagenomics Provides Insight Into the Ecosystem Functioning of the Shark Bay Stromatolites, Western Australia (Journal Article) Frontiers in Microbiology, 9 , pp. 1359, 2018, ISSN: 1664-302X. |
| 100. | Evidence of the Red-Queen Hypothesis from Accelerated Rates of Evolution of Genes Involved in Biotic Interactions in Pneumocystis (Journal Article) Genome Biology and Evolution, 10 (6), pp. 1596-1606, 2018. |
| 99. | GRAM-CNN: a deep learning approach with local context for named entity recognition in biomedical text (Journal Article) Bioinformatics, 34 (9), pp. 1547-1554, 2018. |
| 98. | The SAGA/TREX-2 subunit Sus1 binds widely to transcribed genes and affects mRNA turnover globally (Journal Article) Epigenetics & Chromatin, 11 (1), pp. 13, 2018. |
| 97. | SQANTI: extensive characterization of long-read transcript sequences for quality control in full-length transcriptome identification and quantification (Journal Article) Genome Research, 2018. |
| 96. | Identification and visualization of differential isoform expression in RNA-seq time series (Journal Article) Bioinformatics, 34 (3), pp. 524-526, 2018. |
| 95. | MOSim: Multi-Omics Simulation in R (Journal Article) bioRxiv, pp. 421834, Forthcoming. |
2017 |
|
| 94. | Growth of Chlamydia pneumoniae Is Enhanced in Cell swith Impaired Mitochondrial Function (Journal Article) FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 7 , 2017, ISSN: 2235-2988. |
| 93. | GENOME RESEARCH, 27 (11), pp. 1807-1815, 2017, ISSN: 1088-9051. |
| 92. | A benchmarking of workflows for detecting differential splicing and differential expression at isoform level in human RNA-seq studies (Journal Article) Briefings in Bioinformatics, pp. bbx122, 2017. |
| 91. | Certolizumab Pegol Effectiveness and Retention Rate in Psoriatic Arthritis. Real Life Data (Journal Article) ARTHRITIS & RHEUMATOLOGY, 69 (10), 2017, ISSN: 2326-5191. |
| 90. | Guidelines for Developing Successful Short Advanced Courses in Systems Medicine and Systems Biology (Journal Article) CELL SYSTEMS, 5 (3), pp. 168-175, 2017, ISSN: 2405-4712. |
| 89. | The eBioKit, a stand-alone educational platform for bioinformatics (Journal Article) PLOS COMPUTATIONAL BIOLOGY, 13 (9), 2017, ISSN: 1553-734X. |
| 88. | Dynamic Gene Regulatory Networks of Human Myeloid Differentiation (Journal Article) CELL SYSTEMS, 4 (4), pp. 416+, 2017, ISSN: 2405-4712. |
| 87. | Network Biology of Menstrual Cycle to Understand the Key Drivers of Endometrial Receptivity. (Journal Article) REPRODUCTIVE SCIENCES, 24 (1), pp. 162A, 2017, ISSN: 1933-7191, (64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Orlando, FL, MAR 15-18, 2017). |
| 86. | Identification of miRNA from Bouteloua gracilis, a drought tolerant grass, by deep sequencing and their in silico analysis (Journal Article) COMPUTATIONAL BIOLOGY AND CHEMISTRY, 66 , pp. 26-35, 2017, ISSN: 1476-9271. |
2016 |
|
| 85. | Impacts of abundance of Candidatus Liberibacter on the citrus phyto-microbiome (Journal Article) PHYTOPATHOLOGY, 106 (12, S), pp. 25-26, 2016, ISSN: 0031-949X, (Annual Meeting of the American-Phytopathological-Society (APS), Tampa, FL, JUL 30-AUG 03, 2016). |
| 84. | Making sense of big data in health research: towards an EU action plan (vol 8, pg 71, 2016) (Journal Article) GENOME MEDICINE, 8 , 2016, ISSN: 1756-994X. |
| 83. | RGmatch: matching genomic regions to proximal genes in omics data integration (Journal Article) BMC BIOINFORMATICS, 17 (15), 2016, ISSN: 1471-2105. |
| 82. | Transcriptome modulation during host shift is driven by secondary metabolites in desert Drosophila (Journal Article) MOLECULAR ECOLOGY, 25 (18), pp. 4534-4550, 2016, ISSN: 0962-1083. |
| 81. | A survey of best practices for RNA-seq data analysis (vol 17, 13, 2016) (Journal Article) GENOME BIOLOGY, 17 , 2016, ISSN: 1474-760X. |
| 80. | spongeScan: A web for detecting microRNA binding elements in lncRNA sequences (Journal Article) NUCLEIC ACIDS RESEARCH, 44 (W1), pp. W176-W180, 2016, ISSN: 0305-1048. |
| 79. | Making sense of big data in health research: Towards an EU action plan (Journal Article) GENOME MEDICINE, 8 , 2016, ISSN: 1756-994X. |
| 78. | Separating common from distinctive variation (Journal Article) BMC BIOINFORMATICS, 17 (5), 2016, ISSN: 1471-2105, (Conference on Statistical Methods for Omics Data Integration and Analysis, Heraklion, GREECE, NOV 10-12, 2014). |
| 77. | Qualimap 2: advanced multi-sample quality control for high-throughput sequencing data (Journal Article) BIOINFORMATICS, 32 (2), pp. 292-294, 2016, ISSN: 1367-4803. |
| 76. | A survey of best practices for RNA-seq data analysis (Journal Article) GENOME BIOLOGY, 17 , 2016, ISSN: 1474-760X. |
2015 |
|
| 75. | Data quality aware analysis of differential expression in RNA-seq with NOISeq R/Bioc package (Journal Article) NUCLEIC ACIDS RESEARCH, 43 (21), 2015, ISSN: 0305-1048. |
| 74. | Methylome profiling reveals functions and genes which are differentially methylated in serrated compared to conventional colorectal carcinoma (Journal Article) CLINICAL EPIGENETICS, 7 , 2015, ISSN: 1868-7083. |
| 73. | VETERINARY PARASITOLOGY, 212 (3-4), pp. 111-117, 2015, ISSN: 0304-4017. |
| 72. | RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see resting stage behavior (Journal Article) BMC GENOMICS, 16 , 2015, ISSN: 1471-2164. |
| 71. | Genome-wide changes in histone H3 lysine 27 trimethylation associated with bud dormancy release in peach (Journal Article) TREE GENETICS & GENOMES, 11 (3), 2015, ISSN: 1614-2942. |
| 70. | Two independent epigenetic biomarkers predict survival in neuroblastoma (Journal Article) CLINICAL EPIGENETICS, 7 , 2015, ISSN: 1868-7083. |
2014 |
|
| 69. | BMC GENOMICS, 15 , 2014, ISSN: 1471-2164. |
| 68. | Understanding disease mechanisms with models of signaling pathway activities (Journal Article) BMC SYSTEMS BIOLOGY, 8 , 2014, ISSN: 1752-0509. |
| 67. | A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium (Journal Article) NATURE BIOTECHNOLOGY, 32 (9), pp. 903-914, 2014, ISSN: 1087-0156. |
| 66. | Next maSigPro: updating maSigPro bioconductor package for RNA-seq time series (Journal Article) BIOINFORMATICS, 30 (18), pp. 2598-2602, 2014, ISSN: 1367-4803. |
| 65. | Assessing technical performance in differential gene expression experiments with external spike-in RNA control ratio mixtures (Journal Article) NATURE COMMUNICATIONS, 5 , 2014, ISSN: 2041-1723. |
| 64. | 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) EUROPEAN JOURNAL OF CANCER, 50 (5), pp. S219, 2014, ISSN: 0959-8049. |
| 63. | Relationship between genome and epigenome - challenges and requirements for future research (Journal Article) BMC GENOMICS, 15 , 2014, ISSN: 1471-2164. |
| 62. | Sequencing and functional analysis of the genome of a nematode egg-parasitic fungus, Pochonia chlamydosporia (Journal Article) FUNGAL GENETICS AND BIOLOGY, 65 , pp. 69-80, 2014, ISSN: 1087-1845. |
| 61. | Molecular interactions between sugar beet and Polymyxa betae during its life cycle (Journal Article) ANNALS OF APPLIED BIOLOGY, 164 (2), pp. 244-256, 2014, ISSN: 0003-4746. |
| 60. | Data integration in the era of omics: current and future challenges (Journal Article) BMC SYSTEMS BIOLOGY, 8 (2), 2014, ISSN: 1752-0509. |
| 59. | The common ground of genomics and systems biology (Journal Article) BMC SYSTEMS BIOLOGY, 8 (2), 2014, ISSN: 1752-0509, (High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013). |
| 58. | Pathway network inference from gene expression data (Journal Article) BMC SYSTEMS BIOLOGY, 8 (2), 2014, ISSN: 1752-0509, (High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013). |
| 57. | STATegra EMS: an Experiment Management System for complex next-generation omics experiments (Journal Article) BMC SYSTEMS BIOLOGY, 8 (2), 2014, ISSN: 1752-0509, (High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013). |
| 56. | Methylation Microarray Analysis Identifies Differentially Methylated Genes in Serrated Compared to Conventional Colorectal Carcinomas (Journal Article) LABORATORY INVESTIGATION, 94 (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). |
| 55. | Methylation Microarray Analysis Identifies Differentially Methylated Genes in Serrated Compared to Conventional Colorectal Carcinomas (Journal Article) MODERN PATHOLOGY, 27 (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). |
2013 |
|
| 54. | Defining the Genomic Signature of Totipotency and Pluripotency during Early Human Development (Journal Article) PLOS ONE, 8 (4), 2013, ISSN: 1932-6203. |
| 53. | Expression profiling shows differential molecular pathways and provides potential new diagnostic biomarkers for colorectal serrated adenocarcinoma (Journal Article) INTERNATIONAL JOURNAL OF CANCER, 132 (2), pp. 297-307, 2013, ISSN: 0020-7136. |
2012 |
|
| 52. | METHYLATION STATUS IN NEUROBLASTOMA AND ITS PROGNOSTIC VALUE (Journal Article) PEDIATRIC BLOOD & CANCER, 59 (6, SI), pp. 1053-1054, 2012, ISSN: 1545-5009. |
| 51. | MOLECULAR PLANT PATHOLOGY, 13 (8), pp. 852-864, 2012, ISSN: 1464-6722. |
| 50. | Qualimap: evaluating next-generation sequencing alignment data (Journal Article) BIOINFORMATICS, 28 (20), pp. 2678-2679, 2012, ISSN: 1367-4803. |
| 49. | Development, Characterization and Experimental Validation of a Cultivated Sunflower (Helianthus annuus L.) Gene Expression Oligonucleotide Microarray (Journal Article) PLOS ONE, 7 (10), 2012, ISSN: 1932-6203. |
| 48. | JOURNAL OF EXPERIMENTAL BOTANY, 63 (17), pp. 6079-6091, 2012, ISSN: 0022-0957. |
| 47. | ARSyN: a method for the identification and removal of systematic noise in multifactorial time course microarray experiments (Journal Article) BIOSTATISTICS, 13 (3), pp. 553-566, 2012, ISSN: 1465-4644. |
| 46. | Regulatory proteins in the opportunistic human pathogen Aspergillus fumigatus (Journal Article) MYCOSES, 55 (4, SI), pp. 135-136, 2012, ISSN: 0933-7407. |
| 45. | Identification of yeast genes that confer resistance to chitosan oligosaccharide (COS) using chemogenomics (Journal Article) BMC GENOMICS, 13 , 2012, ISSN: 1471-2164. |
| 44. | Mining of miRNAs and potential targets from gene oriented clusters of transcripts sequences of the anti-malarial plant, Artemisia annua (Journal Article) BIOTECHNOLOGY LETTERS, 34 (4), pp. 737-745, 2012, ISSN: 0141-5492. |
| 43. | Transcriptome Profiling of the Intoxication Response of Tenebrio molitor Larvae to Bacillus thuringiensis Cry3Aa Protoxin (Journal Article) PLOS ONE, 7 (4), 2012, ISSN: 1932-6203. |
| 42. | Transdifferentiation of MALME-3M and MCF-7 Cells toward Adipocyte-like Cells is Dependent on Clathrin-mediated Endocytosis (Journal Article) SPRINGERPLUS, 1 , 2012, ISSN: 2193-1801. |
| 41. | Histone modifications and expression of DAM6 gene in peach are modulated during bud dormancy release in a cultivar-dependent manner (Journal Article) NEW PHYTOLOGIST, 193 (1), pp. 67-80, 2012, ISSN: 0028-646X. |
| 40. | Variable selection for multifactorial genomic data (Journal Article) CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS, 110 (1), pp. 113-122, 2012, ISSN: 0169-7439. |
2011 |
|
| 39. | HUMAN MOLECULAR GENETICS, 20 (24), pp. 4932-4946, 2011, ISSN: 0964-6906. |
| 38. | Differential expression in RNA-seq: A matter of depth (Journal Article) GENOME RESEARCH, 21 (12), pp. 2213-2223, 2011, ISSN: 1088-9051. |
| 37. | Fortunella margarita Transcriptional Reprogramming Triggered by Xanthomonas citri subsp citri (Journal Article) BMC PLANT BIOLOGY, 11 , 2011, ISSN: 1471-2229. |
| 36. | Profiling the venom gland transcriptomes of Costa Rican snakes by 454 pyrosequencing (Journal Article) BMC GENOMICS, 12 , 2011, ISSN: 1471-2164. |
| 35. | B2G-FAR, a species-centered GO annotation repository (Journal Article) BIOINFORMATICS, 27 (7), pp. 919-924, 2011, ISSN: 1367-4803. |
| 34. | Modeling Human Endometrial Decidualization from the Interaction between Proteome and Secretome (Journal Article) JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 96 (3), pp. 706-716, 2011, ISSN: 0021-972X. |
| 33. | Paintomics: a web based tool for the joint visualization of transcriptomics and metabolomics data (Journal Article) BIOINFORMATICS, 27 (1), pp. 137-139, 2011, ISSN: 1367-4803. |
2010 |
|
| 32. | A multiway approach to data integration in systems biology based on Tucker3 and N-PLS (Journal Article) CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS, 104 (1, SI), pp. 101-111, 2010, ISSN: 0169-7439. |
| 31. | Babelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling (Journal Article) NUCLEIC ACIDS RESEARCH, 38 (2), pp. W210-W213, 2010, ISSN: 0305-1048. |
| 30. | Serial Expression Analysis: a web tool for the analysis of serial gene expression data (Journal Article) NUCLEIC ACIDS RESEARCH, 38 (2), pp. W239-W245, 2010, ISSN: 0305-1048. |
| 29. | Initial Genomics of the Human Nucleolus (Journal Article) PLOS GENETICS, 6 (3), 2010, ISSN: 1553-7390. |
| 28. | Hypoxia Promotes Efficient Differentiation of Human Embryonic Stem Cells to Functional Endothelium (Journal Article) STEM CELLS, 28 (3), pp. 407-418, 2010, ISSN: 1066-5099. |
| 27. | SIMAP-a comprehensive database of pre-calculated protein sequence similarities, domains, annotations and clusters (Journal Article) NUCLEIC ACIDS RESEARCH, 38 (1), pp. D223-D226, 2010, ISSN: 0305-1048. |
2009 |
|
| 26. | Membrane transporters and carbon metabolism implicated in chloride homeostasis differentiate salt stress responses in tolerant and sensitive Citrus rootstocks (Journal Article) FUNCTIONAL & INTEGRATIVE GENOMICS, 9 (3), pp. 293-309, 2009, ISSN: 1438-793X. |
| 25. | Functional assessment of time course microarray data (Journal Article) BMC BIOINFORMATICS, 10 , 2009, ISSN: 1471-2105, (European Molecular Biology Network Conference, Martina, ITALY, SEP 18-20, 2008). |
2008 |
|
| 24. | Direct functional assessment of the composite phenotype through multivariate projection strategies (Journal Article) GENOMICS, 92 (6), pp. 373-383, 2008, ISSN: 0888-7543. |
| 23. | Transcriptional Profiling of mRNA Expression in the Mouse Distal Colon (Journal Article) GASTROENTEROLOGY, 135 (6), pp. 2019-2029, 2008, ISSN: 0016-5085. |
| 22. | FOOD AND CHEMICAL TOXICOLOGY, 46 (8), pp. 2616-2628, 2008, ISSN: 0278-6915. |
| 21. | GEPAS, a web-based tool for microarray data analysis and interpretation (Journal Article) NUCLEIC ACIDS RESEARCH, 36 (S), pp. W308-W314, 2008, ISSN: 0305-1048. |
| 20. | Babelomics: advanced functional profiling of transcriptomics, proteomics and genomics experiments (Journal Article) NUCLEIC ACIDS RESEARCH, 36 (S), pp. W341-W346, 2008, ISSN: 0305-1048. |
| 19. | Large-scale Gene Ontology analysis of plant transcriptome-derived sequences retrieved by AFLP technology (Journal Article) BMC GENOMICS, 9 , 2008, ISSN: 1471-2164. |
| 18. | High-throughput functional annotation and data mining with the Blast2GO suite (Journal Article) NUCLEIC ACIDS RESEARCH, 36 (10), pp. 3420-3435, 2008, ISSN: 0305-1048. |
| 17. | Time course profiling of the retinal transcriptome after optic nerve transection and optic nerve crush (Journal Article) MOLECULAR VISION, 14 (126), pp. 1050-1063, 2008, ISSN: 1090-0535. |
2007 |
|
| 16. | Spatial differentiation in the vegetative mycelium of Aspergillus niger (Journal Article) EUKARYOTIC CELL, 6 (12), pp. 2311-2322, 2007, ISSN: 1535-9778. |
| 15. | Transcriptional response of Citrus aurantifolia to infection by Citrus tristeza virus (Journal Article) VIROLOGY, 367 (2), pp. 298-306, 2007, ISSN: 0042-6822. |
| 14. | Discovering gene expression patterns in time course microarray experiments by ANOVA-SCA (Journal Article) BIOINFORMATICS, 23 (14), pp. 1792-1800, 2007, ISSN: 1367-4803. |
| 13. | Analysis of 13000 unique Citrus clusters associated with fruit quality, production and salinity tolerance (Journal Article) BMC GENOMICS, 8 , 2007, ISSN: 1471-2164. |
2006 |
|
| 12. | Development of the GENIPOL European flounder (Platichthys flesus) microarray and determination of temporal transcriptional responses to cadmium at low dose. (Journal Article) ENVIRONMENTAL SCIENCE & TECHNOLOGY, 40 (20), pp. 6479-6488, 2006, ISSN: 0013-936X. |
| 11. | maSigPro: a method to identify significantly differential expression profiles in time-course microarray experiments (Journal Article) BIOINFORMATICS, 22 (9), pp. 1096-1102, 2006, ISSN: 1367-4803. |
2005 |
|
| 10. | Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research (Journal Article) BIOINFORMATICS, 21 (18), pp. 3674-3676, 2005, ISSN: 1367-4803. |
| 9. | Development of a citrus genome-wide EST collection and cDNA microarray as resources for genomic studies (Journal Article) PLANT MOLECULAR BIOLOGY, 57 (3), pp. 375-391, 2005, ISSN: 0167-4412. |
2003 |
|
| 8. | Examining the role of glutamic acid 183 in chloroperoxidase catalysis (Journal Article) JOURNAL OF BIOLOGICAL CHEMISTRY, 278 (16), pp. 13855-13859, 2003, ISSN: 0021-9258. |
2002 |
|
| 7. | Filamentous fungi as cell factories for heterologous protein production (Journal Article) TRENDS IN BIOTECHNOLOGY, 20 (5), pp. 200-206, 2002, ISSN: 0167-7799. |
| 6. | Fungal peroxidases: molecular aspects and applications (Journal Article) JOURNAL OF BIOTECHNOLOGY, 93 (2), pp. 143-158, 2002, ISSN: 0168-1656. |
| 5. | Calnexin overexpression increases manganese peroxidase production in Aspergillus niger (Journal Article) APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 68 (2), pp. 846-851, 2002, ISSN: 0099-2240. |
2001 |
|
| 4. | The secretion pathway in filamentous fungi: A biotechnological view (Journal Article) FUNGAL GENETICS AND BIOLOGY, 33 (3), pp. 155-171, 2001, ISSN: 1087-1845. |
| 3. | C-terminal propeptide of the Caldariomyces fumago chloroperoxidase: an intramolecular chaperone? (Journal Article) FEBS LETTERS, 503 (2-3), pp. 117-120, 2001, ISSN: 0014-5793. |
| 2. | Expression of the Caldariomyces fumago chloroperoxidase in Aspergillus niger and characterization of the recombinant enzyme (Journal Article) JOURNAL OF BIOLOGICAL CHEMISTRY, 276 (21), pp. 17635-17640, 2001, ISSN: 0021-9258. |
2000 |
|
| 1. | Studies on the production of fungal peroxidases in Aspergillus niger (Journal Article) APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 66 (7), pp. 3016-3023, 2000, ISSN: 0099-2240. |
