Publications

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}