{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:08:30Z","timestamp":1791065310424,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1008647","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T00:00:00Z","timestamp":1613520000000}}],"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Novo Nordisk Foundation Center for Biosustainability","award":["NNF10CC1016517"],"award-info":[{"award-number":["NNF10CC1016517"]}]},{"name":"Novo Nordisk Foundation Center for Biosustainability","award":["NNF10CC1016517"],"award-info":[{"award-number":["NNF10CC1016517"]}]},{"name":"Novo Nordisk Foundation Center for Biosustainability","award":["NNF10CC1016517"],"award-info":[{"award-number":["NNF10CC1016517"]}]},{"name":"Novo Nordisk Foundation Center for Biosustainability","award":["NNF10CC1016517"],"award-info":[{"award-number":["NNF10CC1016517"]}]},{"name":"Novo Nordisk Foundation Center for Biosustainability","award":["NNF10CC1016517"],"award-info":[{"award-number":["NNF10CC1016517"]}]},{"name":"Novo Nordisk Foundation Center for Biosustainability","award":["NNF10CC1016517"],"award-info":[{"award-number":["NNF10CC1016517"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    The availability of bacterial transcriptomes has dramatically increased in recent years. This data deluge could result in detailed inference of underlying regulatory networks, but the diversity of experimental platforms and protocols introduces critical biases that could hinder scalable analysis of existing data. Here, we show that the underlying structure of the\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>coli<\/jats:italic>\n                    transcriptome, as determined by Independent Component Analysis (ICA), is conserved across multiple independent datasets, including both RNA-seq and microarray datasets. We subsequently combined five transcriptomics datasets into a large compendium containing over 800 expression profiles and discovered that its underlying ICA-based structure was still comparable to that of the individual datasets. With this understanding, we expanded our analysis to over 3,000\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>coli<\/jats:italic>\n                    expression profiles and predicted three high-impact regulons that respond to oxidative stress, anaerobiosis, and antibiotic treatment. ICA thus enables deep analysis of disparate data to uncover new insights that were not visible in the individual datasets.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1008647","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T15:52:16Z","timestamp":1612281136000},"page":"e1008647","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":43,"title":["Independent component analysis recovers consistent regulatory signals from disparate datasets"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8293-3909","authenticated-orcid":true,"given":"Anand V.","family":"Sastry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0152-1580","authenticated-orcid":true,"given":"Alyssa","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1422-1712","authenticated-orcid":true,"given":"David","family":"Heckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3732-2463","authenticated-orcid":true,"given":"Saugat","family":"Poudel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2525-0818","authenticated-orcid":true,"given":"Erol","family":"Kavvas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard O.","family":"Palsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"pcbi.1008647.ref001","doi-asserted-by":"crossref","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets\u2014update","volume":"41","author":"T Barrett","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008647.ref002","doi-asserted-by":"crossref","first-page":"D711","DOI":"10.1093\/nar\/gky964","article-title":"ArrayExpress update\u2014from bulk to single-cell expression data","volume":"47","author":"A Athar","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008647.ref003","doi-asserted-by":"crossref","first-page":"D620","DOI":"10.1093\/nar\/gkv1251","article-title":"COLOMBOS v3.0: leveraging gene expression compendia for cross-species analyses","volume":"44","author":"M Moretto","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008647.ref004","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.cell.2014.06.049","article-title":"Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin","volume":"158","author":"KA Hoadley","year":"2014","journal-title":"Cell"},{"key":"pcbi.1008647.ref005","doi-asserted-by":"crossref","first-page":"e78644","DOI":"10.1371\/journal.pone.0078644","article-title":"Comparison of RNA-Seq and microarray in transcriptome profiling of activated T cells.","volume":"9","author":"S Zhao","year":"2014","journal-title":"PLoS One."},{"key":"pcbi.1008647.ref006","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1038\/nbt1239","article-title":"The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements.","volume":"24","author":"MAQC Consortium","year":"2006","journal-title":"Nat Biotechnol"},{"key":"pcbi.1008647.ref007","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1038\/nbt.2957","article-title":"A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium.","volume":"32","author":"SEQC\/MAQC-III Consortium.","year":"2014","journal-title":"Nat Biotechnol"},{"key":"pcbi.1008647.ref008","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/nbt.2702","article-title":"Reproducibility of high-throughput mRNA and small RNA sequencing across laboratories","volume":"31","author":"PAC \u2018t Hoen","year":"2013","journal-title":"Nat Biotechnol"},{"key":"pcbi.1008647.ref009","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.tibtech.2017.02.012","article-title":"Why Batch Effects Matter in Omics Data, and How to Avoid Them","volume":"35","author":"WWB Goh","year":"2017","journal-title":"Trends Biotechnol"},{"key":"pcbi.1008647.ref010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"DW Huang","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008647.ref011","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"MV Kuleshov","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008647.ref012","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13059-016-0940-1","article-title":"A benchmark for RNA-seq quantification pipelines","volume":"17","author":"M Teng","year":"2016","journal-title":"Genome Biol"},{"key":"pcbi.1008647.ref013","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/1471-2105-14-91","article-title":"A comparison of methods for differential expression analysis of RNA-seq data","volume":"14","author":"C Soneson","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"pcbi.1008647.ref014","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.tig.2018.07.003","article-title":"Enter the Matrix: Factorization Uncovers Knowledge from Omics","volume":"34","author":"GL Stein-O\u2019Brien","year":"2018","journal-title":"Trends Genet"},{"key":"pcbi.1008647.ref015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-biodatasci-072018-021348","article-title":"Discovering Pathway and Cell Type Signatures in Transcriptomic Compendia with Machine Learning.","volume":"2","author":"GP Way","year":"2019","journal-title":"Annu Rev Biomed Data Sci"},{"key":"pcbi.1008647.ref016","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20184414","article-title":"Independent Component Analysis for Unraveling the Complexity of Cancer Omics Datasets.","volume":"20","author":"N Sompairac","year":"2019","journal-title":"Int J Mol Sci."},{"key":"pcbi.1008647.ref017","doi-asserted-by":"crossref","first-page":"501","DOI":"10.2144\/000112950","article-title":"A review of independent component analysis application to microarray gene expression data","volume":"45","author":"W Kong","year":"2008","journal-title":"Biotechniques"},{"key":"pcbi.1008647.ref018","doi-asserted-by":"crossref","first-page":"e1004122","DOI":"10.1371\/journal.pgen.1004122","article-title":"Coherent functional modules improve transcription factor target identification, cooperativity prediction, and disease association.","volume":"10","author":"KJ Karczewski","year":"2014","journal-title":"PLoS Genet"},{"key":"pcbi.1008647.ref019","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.jbi.2010.07.001","article-title":"Independent component analysis: mining microarray data for fundamental human gene expression modules.","volume":"43","author":"JM Engreitz","year":"2010","journal-title":"J Biomed Inform."},{"key":"pcbi.1008647.ref020","doi-asserted-by":"crossref","first-page":"e161","DOI":"10.1371\/journal.pcbi.0030161","article-title":"Elucidating the altered transcriptional programs in breast cancer using independent component analysis.","volume":"3","author":"AE Teschendorff","year":"2007","journal-title":"PLoS Comput Biol."},{"key":"pcbi.1008647.ref021","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.celrep.2014.10.035","article-title":"Independent component analysis uncovers the landscape of the bladder tumor transcriptome and reveals insights into luminal and basal subtypes.","volume":"9","author":"A Biton","year":"2014","journal-title":"Cell Rep."},{"key":"pcbi.1008647.ref022","doi-asserted-by":"crossref","first-page":"S169","DOI":"10.1074\/mcp.TIR119.001442","article-title":"Extracting Pathway-level Signatures from Proteogenomic Data in Breast Cancer Using Independent Component Analysis","volume":"18","author":"W Liu","year":"2019","journal-title":"Mol Cell Proteomics"},{"key":"pcbi.1008647.ref023","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/s41467-018-03424-4","article-title":"A comprehensive evaluation of module detection methods for gene expression data","volume":"9","author":"W Saelens","year":"2018","journal-title":"Nat Commun"},{"key":"pcbi.1008647.ref024","doi-asserted-by":"crossref","first-page":"5536","DOI":"10.1038\/s41467-019-13483-w","article-title":"The Escherichia coli transcriptome mostly consists of independently regulated modules.","volume":"10","author":"AV Sastry","year":"2019","journal-title":"Nat Commun."},{"key":"pcbi.1008647.ref025","doi-asserted-by":"crossref","first-page":"25287","DOI":"10.1073\/pnas.1909987116","article-title":"Adaptive evolution reveals a tradeoff between growth rate and oxidative stress during naphthoquinone-based aerobic respiration","volume":"116","author":"A Anand","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pcbi.1008647.ref026","article-title":"OxyR is a convergent target for mutations acquired during adaptation to oxidative stress-prone metabolic states","author":"A Anand","year":"2019","journal-title":"Mol Biol Evol"},{"key":"pcbi.1008647.ref027","first-page":"2020","article-title":"Decomposition of transcriptional responses provides insights into differential antibiotic susceptibility.","author":"AV Sastry","year":"2020","journal-title":"bioRxiv."},{"key":"pcbi.1008647.ref028","first-page":"2020","article-title":"Synthesis of the novel transporter YdhC, is regulated by the YdhB transcription factor controlling adenosine and adenine uptake.","author":"IA Rodionova","year":"2020","journal-title":"bioRxiv."},{"key":"pcbi.1008647.ref029","first-page":"2020","article-title":"Revealing 29 sets of independently modulated genes in Staphylococcus aureus, their regulators and role in key physiological responses.","author":"S Poudel","year":"2020","journal-title":"bioRxiv"},{"key":"pcbi.1008647.ref030","first-page":"2020","article-title":"Machine learning uncovers independently regulated modules in the Bacillus subtilis transcriptome.","author":"K Rychel","year":"2020","journal-title":"bioRxiv."},{"key":"pcbi.1008647.ref031","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1093\/nar\/gkz030","article-title":"The y-ome defines the 35% of Escherichia coli genes that lack experimental evidence of function","volume":"47","author":"S Ghatak","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008647.ref032","doi-asserted-by":"crossref","first-page":"e2006643","DOI":"10.1371\/journal.pbio.2006643","article-title":"Large-scale investigation of the reasons why potentially important genes are ignored","volume":"16","author":"T Stoeger","year":"2018","journal-title":"PLoS Biol"},{"key":"pcbi.1008647.ref033","article-title":"Assessing reproducibility of matrix factorization methods in independent transcriptomes","author":"L Cantini","year":"2019","journal-title":"Bioinformatics"},{"key":"pcbi.1008647.ref034","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/s41564-018-0164-0","article-title":"Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides","volume":"3","author":"V L\u00e1z\u00e1r","year":"2018","journal-title":"Nat Microbiol"},{"key":"pcbi.1008647.ref035","doi-asserted-by":"crossref","first-page":"e8","DOI":"10.1371\/journal.pbio.0050008","article-title":"Large-scale mapping and validation of Escherichia coli transcriptional regulation from a compendium of expression profiles","volume":"5","author":"JJ Faith","year":"2007","journal-title":"PLoS Biol"},{"key":"pcbi.1008647.ref036","doi-asserted-by":"crossref","first-page":"e1004264","DOI":"10.1371\/journal.pgen.1004264","article-title":"Determining the control circuitry of redox metabolism at the genome-scale","volume":"10","author":"S Federowicz","year":"2014","journal-title":"PLoS Genet"},{"key":"pcbi.1008647.ref037","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature02456","article-title":"Integrating high-throughput and computational data elucidates bacterial networks","volume":"429","author":"MW Covert","year":"2004","journal-title":"Nature"},{"key":"pcbi.1008647.ref038","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1101\/gr.3832305","article-title":"Parallel adaptive evolution cultures of Escherichia coli lead to convergent growth phenotypes with different gene expression states","volume":"15","author":"SS Fong","year":"2005","journal-title":"Genome Res"},{"key":"pcbi.1008647.ref039","doi-asserted-by":"crossref","first-page":"11096","DOI":"10.1073\/pnas.1811971115","article-title":"Characterizing posttranslational modifications in prokaryotic metabolism using a multiscale workflow","volume":"115","author":"E Brunk","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pcbi.1008647.ref040","doi-asserted-by":"crossref","first-page":"20500","DOI":"10.1073\/pnas.0911253107","article-title":"RNA polymerase mutants found through adaptive evolution reprogram Escherichia coli for optimal growth in minimal media","volume":"107","author":"TM Conrad","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pcbi.1008647.ref041","doi-asserted-by":"crossref","first-page":"6529","DOI":"10.1128\/AEM.01178-10","article-title":"Deletion of genes encoding cytochrome oxidases and quinol monooxygenase blocks the aerobic-anaerobic shift in Escherichia coli K-12 MG1655","volume":"76","author":"VA Portnoy","year":"2010","journal-title":"Appl Environ Microbiol"},{"key":"pcbi.1008647.ref042","doi-asserted-by":"crossref","first-page":"6456","DOI":"10.1093\/nar\/gkr307","article-title":"The PurR regulon in Escherichia coli K-12 MG1655","volume":"39","author":"B-K Cho","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008647.ref043","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1126\/science.1216861","article-title":"Network context and selection in the evolution to enzyme specificity","volume":"337","author":"H Nam","year":"2012","journal-title":"Science"},{"key":"pcbi.1008647.ref044","article-title":"Systematic discovery of uncharacterized transcription factors in Escherichia coli K-12 MG1655","author":"Y Gao","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008647.ref045","article-title":"Multi-omic characterization of E. coli for the purpose of microbial-based production.","author":"WKJ Tan","year":"2019","journal-title":"UC San Diego."},{"key":"pcbi.1008647.ref046","doi-asserted-by":"crossref","first-page":"e101850","DOI":"10.1371\/journal.pone.0101850","article-title":"Quickly finding orthologs as reciprocal best hits with BLAT, LAST, and UBLAST: how much do we miss?","volume":"9","author":"N Ward","year":"2014","journal-title":"PLoS One"},{"key":"pcbi.1008647.ref047","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/msb.2013.57","article-title":"Bacterial evolution of antibiotic hypersensitivity","volume":"9","author":"V L\u00e1z\u00e1r","year":"2013","journal-title":"Mol Syst Biol"},{"key":"pcbi.1008647.ref048","article-title":"Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network","author":"V L\u00e1z\u00e1r","year":"2014","journal-title":"Nature Communications"},{"key":"pcbi.1008647.ref049","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1128\/AAC.49.7.2746-2752.2005","article-title":"Constitutive soxR mutations contribute to multiple-antibiotic resistance in clinical Escherichia coli isolates","volume":"49","author":"A Koutsolioutsou","year":"2005","journal-title":"Antimicrob Agents Chemother"},{"key":"pcbi.1008647.ref050","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1111\/mmi.12429","article-title":"Lon protease inactivation, or translocation of the lon gene, potentiate bacterial evolution to antibiotic resistance","volume":"90","author":"H Nicoloff","year":"2013","journal-title":"Mol Microbiol"},{"key":"pcbi.1008647.ref051","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1186\/s12864-017-4112-9","article-title":"Determining the optimal number of independent components for reproducible transcriptomic data analysis","volume":"18","author":"U Kairov","year":"2017","journal-title":"BMC Genomics"},{"key":"pcbi.1008647.ref052","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.mib.2008.02.001","article-title":"Control of bacterial transcription, translation and replication by (p)ppGpp.","volume":"11","author":"A Srivatsan","year":"2008","journal-title":"Curr Opin Microbiol"},{"key":"pcbi.1008647.ref053","doi-asserted-by":"crossref","first-page":"8310","DOI":"10.1073\/pnas.1819682116","article-title":"Genome-wide effects on Escherichia coli transcription from ppGpp binding to its two sites on RNA polymerase","volume":"116","author":"P Sanchez-Vazquez","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pcbi.1008647.ref054","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.cels.2016.04.003","article-title":"Global Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution.","volume":"2","author":"J Utrilla","year":"2016","journal-title":"Cell Syst"},{"key":"pcbi.1008647.ref055","doi-asserted-by":"crossref","first-page":"e1004127","DOI":"10.1371\/journal.pcbi.1004127","article-title":"Microbial forensics: predicting phenotypic characteristics and environmental conditions from large-scale gene expression profiles","volume":"11","author":"M Kim","year":"2015","journal-title":"PLoS Comput Biol"},{"key":"pcbi.1008647.ref056","article-title":"Global transcriptional regulatory network for Escherichia coli robustly connects gene expression to transcription factor activities","author":"X Fang","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pcbi.1008647.ref057","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1099\/mic.0.000026","article-title":"Cooperative regulation of the common target genes between H2O2-sensing YedVW and Cu2+-sensing CusSR in Escherichia coli","volume":"161","author":"H Urano","year":"2015","journal-title":"Microbiology"},{"key":"pcbi.1008647.ref058","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nature15764","article-title":"Repairing oxidized proteins in the bacterial envelope using respiratory chain electrons","volume":"528","author":"A Gennaris","year":"2015","journal-title":"Nature"},{"key":"pcbi.1008647.ref059","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.bbabio.2012.11.007","article-title":"Molybdenum enzymes, their maturation and molybdenum cofactor biosynthesis in Escherichia coli","volume":"1827","author":"C Iobbi-Nivol","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"pcbi.1008647.ref060","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1046\/j.1365-2958.2003.03815.x","article-title":"The RcsC sensor kinase is required for normal biofilm formation in Escherichia coli K-12 and controls the expression of a regulon in response to growth on a solid surface","volume":"50","author":"L Ferri\u00e8res","year":"2003","journal-title":"Mol Microbiol"},{"key":"pcbi.1008647.ref061","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.mib.2010.09.002","article-title":"Polymyxins and their novel derivatives.","volume":"13","author":"M Vaara","year":"2010","journal-title":"Curr Opin Microbiol"},{"key":"pcbi.1008647.ref062","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/gb-2009-10-3-r25","article-title":"Ultrafast and memory-efficient alignment of short DNA sequences to the human genome","volume":"10","author":"B Langmead","year":"2009","journal-title":"Genome Biol"},{"key":"pcbi.1008647.ref063","doi-asserted-by":"crossref","first-page":"e1003118","DOI":"10.1371\/journal.pcbi.1003118","article-title":"Software for computing and annotating genomic ranges.","volume":"9","author":"M Lawrence","year":"2013","journal-title":"PLoS Comput Biol"},{"key":"pcbi.1008647.ref064","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"key":"pcbi.1008647.ref065","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/bioinformatics\/btg405","article-title":"affy\u2014analysis of Affymetrix GeneChip data at the probe level","volume":"20","author":"L Gautier","year":"2004","journal-title":"Bioinformatics"},{"key":"pcbi.1008647.ref066","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkw1003","article-title":"The EcoCyc database: reflecting new knowledge about Escherichia coli K-12","volume":"45","author":"IM Keseler","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008647.ref067","doi-asserted-by":"crossref","first-page":"D286","DOI":"10.1093\/nar\/gkv1248","article-title":"eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences","volume":"44","author":"J Huerta-Cepas","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008647.ref068","doi-asserted-by":"crossref","first-page":"D330","DOI":"10.1093\/nar\/gky1055","article-title":"The Gene Ontology Resource: 20 years and still GOing strong.","author":"The Gene Ontology Consortium, The Gene Ontology Consortium.","year":"2019","journal-title":"Nucleic Acids Research"},{"key":"pcbi.1008647.ref069","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s12915-018-0555-y","article-title":"A unified resource for transcriptional regulation in Escherichia coli K-12 incorporating high-throughput-generated binding data into RegulonDB version 10.0.","volume":"16","author":"A Santos-Zavaleta","year":"2018","journal-title":"BMC Biol."},{"key":"pcbi.1008647.ref070","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1128\/MMBR.00001-08","article-title":"Regulation of pyrimidine biosynthetic gene expression in bacteria: repression without repressors","volume":"72","author":"CL Turnbough","year":"2008","journal-title":"Microbiol Mol Biol Rev"},{"key":"pcbi.1008647.ref071","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1002\/1097-024X(200009)30:11<1203::AID-SPE338>3.0.CO;2-N","article-title":"An open graph visualization system and its applications to software engineering","volume":"30","author":"ER Gansner","year":"2000","journal-title":"Softw Pract Exp"},{"key":"pcbi.1008647.ref072","first-page":"2825","article-title":"Scikit-learn: Machine Learning in Python.","volume":"12","author":"F Pedregosa","year":"2011","journal-title":"J Mach Learn Res."}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1008647","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T00:00:00Z","timestamp":1613520000000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008647","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T16:11:09Z","timestamp":1613578269000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008647"}},"subtitle":[],"editor":[{"given":"Kiran Raosaheb","family":"Patil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,2,2]]},"references-count":72,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1008647","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.04.26.061978","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,2]]}}}