{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:41:17Z","timestamp":1772138477733,"version":"3.50.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"W1","license":[{"start":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T00:00:00Z","timestamp":1589155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 LM012736"],"award-info":[{"award-number":["R01 LM012736"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 MH113005"],"award-info":[{"award-number":["R01 MH113005"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K99 MH120050"],"award-info":[{"award-number":["K99 MH120050"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Co-expression analysis has provided insight into gene function in organisms from Arabidopsis to zebrafish. Comparison across species has the potential to enrich these results, for example by prioritizing among candidate human disease genes based on their network properties or by finding alternative model systems where their co-expression is conserved. Here, we present CoCoCoNet as a tool for identifying conserved gene modules and comparing co-expression networks. CoCoCoNet is a resource for both data and methods, providing gold standard networks and sophisticated tools for on-the-fly comparative analyses across 14 species. We show how CoCoCoNet can be used in two use cases. In the first, we demonstrate deep conservation of a nucleolus gene module across very divergent organisms, and in the second, we show how the heterogeneity of autism mechanisms in humans can be broken down by functional groups and translated to model organisms. CoCoCoNet is free to use and available to all at https:\/\/milton.cshl.edu\/CoCoCoNet, with data and R scripts available at ftp:\/\/milton.cshl.edu\/data.<\/jats:p>","DOI":"10.1093\/nar\/gkaa348","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T15:08:54Z","timestamp":1587740934000},"page":"W566-W571","source":"Crossref","is-referenced-by-count":48,"title":["CoCoCoNet: conserved and comparative co-expression across a diverse set of species"],"prefix":"10.1093","volume":"48","author":[{"given":"John","family":"Lee","sequence":"first","affiliation":[{"name":"Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, 500 Sunnyside Blvd., Woodbury, NY 11797, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manthan","family":"Shah","sequence":"first","affiliation":[{"name":"Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, 500 Sunnyside Blvd., Woodbury, NY 11797, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4701-3020","authenticated-orcid":false,"given":"Sara","family":"Ballouz","sequence":"first","affiliation":[{"name":"Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, 500 Sunnyside Blvd., Woodbury, NY 11797, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Crow","sequence":"first","affiliation":[{"name":"Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, 500 Sunnyside Blvd., Woodbury, NY 11797, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0936-9774","authenticated-orcid":false,"given":"Jesse","family":"Gillis","sequence":"first","affiliation":[{"name":"Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, 500 Sunnyside Blvd., Woodbury, NY 11797, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,5,11]]},"reference":[{"key":"2020062614045194900_B1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2202\/1544-6115.1128","article-title":"A general framework for weighted gene co-expression network analysis","volume":"4","author":"Zhang","year":"2005","journal-title":"Stat. Appl. Genet. Mol. Biol."},{"key":"2020062614045194900_B2","doi-asserted-by":"crossref","first-page":"14863","DOI":"10.1073\/pnas.95.25.14863","article-title":"Cluster analysis and display of genome-wide expression patterns","volume":"95","author":"Eisen","year":"1998","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2020062614045194900_B3","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1471-2105-5-18","article-title":"Quantifying the relationship between co-expression, co-regulation and gene function","volume":"5","author":"Allocco","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"2020062614045194900_B4","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1093\/bioinformatics\/btv118","article-title":"Guidance for RNA-seq co-expression network construction and analysis: safety in numbers","volume":"31","author":"Ballouz","year":"2015","journal-title":"Bioinformatics"},{"key":"2020062614045194900_B5","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13059-016-0964-6","article-title":"Exploiting single-cell expression to characterize co-expression replicability","volume":"17","author":"Crow","year":"2016","journal-title":"Genome Biol."},{"key":"2020062614045194900_B6","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1186\/1471-2105-10-346","article-title":"Arabidopsis gene co-expression network and its functional modules","volume":"10","author":"Mao","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"2020062614045194900_B7","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1007\/s00425-019-03102-9","article-title":"Gene co-expression network analysis identifies trait-related modules in Arabidopsis thaliana","volume":"249","author":"Liu","year":"2019","journal-title":"Planta"},{"key":"2020062614045194900_B8","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1186\/s12862-015-0534-7","article-title":"A comparison of human and mouse gene co-expression networks reveals conservation and divergence at the tissue, pathway and disease levels","volume":"15","author":"Monaco","year":"2015","journal-title":"BMC Evol. Biol."},{"key":"2020062614045194900_B9","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1471-2164-7-40","article-title":"Gene connectivity, function, and sequence conservation: predictions from modular yeast co-expression networks","volume":"7","author":"Carlson","year":"2006","journal-title":"BMC Genomics"},{"key":"2020062614045194900_B10","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature10110","article-title":"Transcriptomic analysis of autistic brain reveals convergent molecular pathology","volume":"474","author":"Voineagu","year":"2011","journal-title":"Nature"},{"key":"2020062614045194900_B11","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.ygeno.2018.05.005","article-title":"Gene co-expression network analysis for identifying genetic markers in Parkinson\u2019s disease: a three-way comparative approach","volume":"111","author":"George","year":"2019","journal-title":"Genomics"},{"key":"2020062614045194900_B12","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1161\/CIRCGENETICS.110.941757","article-title":"Gene coexpression network topology of cardiac development, hypertrophy, and failure","volume":"4","author":"Dewey","year":"2011","journal-title":"Circ. Cardiovasc. Genet."},{"key":"2020062614045194900_B13","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.3390\/ijms19092500","article-title":"Co-expression network analysis identifies miRNA\u2013mRNA networks potentially regulating milk traits and blood metabolites","volume":"19","author":"Ammah","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"2020062614045194900_B14","doi-asserted-by":"crossref","first-page":"e012941","DOI":"10.1161\/JAHA.119.012941","article-title":"Spatiotemporal gene coexpression and regulation in mouse cardiomyocytes of early cardiac morphogenesis","volume":"8","author":"Liu","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"2020062614045194900_B15","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/gb-2008-9-s1-s2","article-title":"A critical assessment of Mus musculus gene function prediction using integrated genomic evidence","volume":"9","author":"Pena-Castillo","year":"2008","journal-title":"Genome Biol."},{"key":"2020062614045194900_B16","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s13059-016-1037-6","article-title":"An expanded evaluation of protein function prediction methods shows an improvement in accuracy","volume":"17","author":"Jiang","year":"2016","journal-title":"Genome Biol."},{"key":"2020062614045194900_B17","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.tplants.2016.12.011","article-title":"Beyond genomics: studying evolution with gene coexpression networks","volume":"22","author":"Ruprecht","year":"2017","journal-title":"Trends Plant Sci."},{"key":"2020062614045194900_B18","doi-asserted-by":"crossref","first-page":"D55","DOI":"10.1093\/nar\/gky1155","article-title":"COXPRESdb v7: a gene coexpression database for 11 animal species supported by 23 coexpression platforms for technical evaluation and evolutionary inference","volume":"47","author":"Obayashi","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2020062614045194900_B19","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1093\/pcp\/pcx209","article-title":"ATTED-II in 2018: a plant coexpression database based on investigation of the statistical property of the mutual rank index","volume":"59","author":"Obayashi","year":"2018","journal-title":"Plant Cell Physiol."},{"key":"2020062614045194900_B20","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1186\/1471-2164-13-535","article-title":"GeneFriends: an online co-expression analysis tool to identify novel gene targets for aging and complex diseases","volume":"13","author":"van\u00a0Dam","year":"2012","journal-title":"BMC Genomics"},{"key":"2020062614045194900_B21","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/978-1-4939-6658-5_12","article-title":"PlaNet: comparative co-expression network analyses for plants","volume":"1533","author":"Proost","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"2020062614045194900_B22","doi-asserted-by":"crossref","first-page":"D848","DOI":"10.1093\/nar\/gkv1155","article-title":"MouseNet v2: a database of gene networks for studying the laboratory mouse and eight other model vertebrates","volume":"44","author":"Kim","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2020062614045194900_B23","doi-asserted-by":"crossref","first-page":"W60","DOI":"10.1093\/nar\/gky311","article-title":"GeneMANIA update 2018","volume":"46","author":"Franz","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2020062614045194900_B24","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/nar\/gkq1019","article-title":"The Sequence Read Archive","volume":"39","author":"Leinonen","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2020062614045194900_B25","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1471-2105-14-19","article-title":"SRAdb: query and use public next-generation sequencing data from within R","volume":"14","author":"Zhu","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2020062614045194900_B26","doi-asserted-by":"crossref","first-page":"D745","DOI":"10.1093\/nar\/gky1113","article-title":"Ensembl 2019","volume":"47","author":"Cunningham","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2020062614045194900_B27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2020062614045194900_B28","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"2020062614045194900_B29","doi-asserted-by":"crossref","first-page":"D330","DOI":"10.1093\/nar\/gky1055","article-title":"The Gene Ontology resource: 20 years and still GOing strong","volume":"47","author":"The","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2020062614045194900_B30","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.1093\/bioinformatics\/bti525","article-title":"BioMart and Bioconductor: a powerful link between biological databases and microarray data analysis","volume":"21","author":"Durinck","year":"2005","journal-title":"Bioinformatics"},{"key":"2020062614045194900_B31","doi-asserted-by":"crossref","first-page":"D807","DOI":"10.1093\/nar\/gky1053","article-title":"OrthoDB v10: sampling the diversity of animal, plant, fungal, protist, bacterial and viral genomes for evolutionary and functional annotations of orthologs","volume":"47","author":"Kriventseva","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2020062614045194900_B32","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/35001165","article-title":"Guilt-by-association goes global","volume":"403","author":"Oliver","year":"2000","journal-title":"Nature"},{"key":"2020062614045194900_B33","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1093\/bioinformatics\/btw695","article-title":"EGAD: ultra-fast functional analysis of gene networks","volume":"33","author":"Ballouz","year":"2017","journal-title":"Bioinformatics"},{"key":"2020062614045194900_B34","doi-asserted-by":"crossref","first-page":"e17258","DOI":"10.1371\/journal.pone.0017258","article-title":"The impact of multifunctional genes on \u2018guilt by association\u2019 analysis","volume":"6","author":"Gillis","year":"2011","journal-title":"PLoS One"},{"key":"2020062614045194900_B35","article-title":"shiny: web application framework for R","author":"Chang","year":"2019"},{"key":"2020062614045194900_B36","article-title":"visNetwork: network visualization using \u2018vis.js\u2019 library","author":"Almende","year":"2019"},{"key":"2020062614045194900_B37","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/324446a0","article-title":"A hierarchical O(N log N) force-calculation algorithm","volume":"324","author":"Barnes","year":"1986","journal-title":"Nature"},{"key":"2020062614045194900_B38","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: Elegant Graphics for Data Analysis","author":"Wickham","year":"2016"},{"key":"2020062614045194900_B39","author":"Sievert","year":"2018"},{"key":"2020062614045194900_B40","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1073\/pnas.1222878110","article-title":"Genomic responses in mouse models poorly mimic human inflammatory diseases","volume":"110","author":"Seok","year":"2013","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2020062614045194900_B41","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1073\/pnas.1401965111","article-title":"Genomic responses in mouse models greatly mimic human inflammatory diseases","volume":"112","author":"Takao","year":"2015","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2020062614045194900_B42","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/nrd1470","article-title":"Can the pharmaceutical industry reduce attrition rates?","volume":"3","author":"Kola","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"2020062614045194900_B43","doi-asserted-by":"crossref","first-page":"e10887","DOI":"10.1371\/journal.pone.0010887","article-title":"Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes","volume":"5","author":"Bruining","year":"2010","journal-title":"PLoS One"},{"key":"2020062614045194900_B44","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.neubiorev.2016.06.013","article-title":"Genetic heterogeneity in autism: from single gene to a pathway perspective","volume":"68","author":"An","year":"2016","journal-title":"Neurosci. Biobehav. Rev"},{"key":"2020062614045194900_B45","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/nrneurol.2013.278","article-title":"Disentangling the heterogeneity of autism spectrum disorder through genetic findings","volume":"10","author":"Jeste","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"2020062614045194900_B46","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.cell.2019.12.036","article-title":"Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism","volume":"180","author":"Satterstrom","year":"(2020","journal-title":"Cell"},{"key":"2020062614045194900_B47","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nature13772","article-title":"Synaptic, transcriptional and chromatin genes disrupted in autism","volume":"515","author":"De\u00a0Rubeis","year":"2014","journal-title":"Nature"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/48\/W1\/W566\/33433140\/gkaa348.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/48\/W1\/W566\/33433140\/gkaa348.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T05:34:54Z","timestamp":1696052094000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/48\/W1\/W566\/5835815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,11]]},"references-count":47,"journal-issue":{"issue":"W1","published-online":{"date-parts":[[2020,5,11]]},"published-print":{"date-parts":[[2020,7,2]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkaa348","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.04.21.053900","asserted-by":"object"}]},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,7,2]]},"published":{"date-parts":[[2020,5,11]]}}}