{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T12:15:34Z","timestamp":1783426534134,"version":"3.54.6"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: RNA-seq co-expression analysis is in its infancy and reasonable practices remain poorly defined. We assessed a variety of RNA-seq expression data to determine factors affecting functional connectivity and topology in co-expression networks.<\/jats:p>\n               <jats:p>Results: We examine RNA-seq co-expression data generated from 1970 RNA-seq samples using a Guilt-By-Association framework, in which genes are assessed for the tendency of co-expression to reflect shared function. Minimal experimental criteria to obtain performance on par with microarrays were &amp;gt;20 samples with read depth &amp;gt;10\u2009M per sample. While the aggregate network constructed shows good performance (area under the receiver operator characteristic curve \u223c0.71), the dependency on number of experiments used is nearly identical to that present in microarrays, suggesting thousands of samples are required to obtain \u2018gold-standard\u2019 co-expression. We find a major topological difference between RNA-seq and microarray co-expression in the form of low overlaps between hub-like genes from each network due to changes in the correlation of expression noise within each technology.<\/jats:p>\n               <jats:p>Contact: \u00a0jgillis@cshl.edu or sballouz@cshl.edu<\/jats:p>\n               <jats:p>Supplementary information: Networks are available at: http:\/\/gillislab.labsites.cshl.edu\/supplements\/rna-seq-networks\/ and supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv118","type":"journal-article","created":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T15:34:19Z","timestamp":1424964859000},"page":"2123-2130","source":"Crossref","is-referenced-by-count":209,"title":["Guidance for RNA-seq co-expression network construction and analysis: safety in numbers"],"prefix":"10.1093","volume":"31","author":[{"given":"S.","family":"Ballouz","sequence":"first","affiliation":[{"name":"Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, 500 Sunnyside Boulevard Woodbury, NY 11797, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Verleyen","sequence":"additional","affiliation":[{"name":"Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, 500 Sunnyside Boulevard Woodbury, NY 11797, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Gillis","sequence":"additional","affiliation":[{"name":"Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, 500 Sunnyside Boulevard Woodbury, NY 11797, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,28]]},"reference":[{"key":"2023020202150858600_btv118-B1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"2023020202150858600_btv118-B2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1534\/genetics.110.114983","article-title":"Statistical design and analysis of RNA sequencing data","volume":"185","author":"Auer","year":"2010","journal-title":"Genetics"},{"key":"2023020202150858600_btv118-B3","article-title":"BrainSpan: Atlas of the Developing Human Brain [Internet]","author":"BrainSpan atlas","year":"2011"},{"key":"2023020202150858600_btv118-B4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach. Learn."},{"key":"2023020202150858600_btv118-B5","first-page":"551","article-title":"Online passive-aggressive algorithms","volume":"7","author":"Crammer","year":"2006","journal-title":"J. Mach. Learn. Res."},{"key":"2023020202150858600_btv118-B6","doi-asserted-by":"crossref","first-page":"D691","DOI":"10.1093\/nar\/gkq1018","article-title":"Reactome: a database of reactions, pathways and biological processes","volume":"39","author":"Croft","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2023020202150858600_btv118-B7","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1093\/bioinformatics\/btm254","article-title":"GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor","volume":"23","author":"Davis","year":"2007","journal-title":"Bioinformatics"},{"key":"2023020202150858600_btv118-B8","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":"2023020202150858600_btv118-B9","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":"Faith","year":"2007","journal-title":"PLoS Biol."},{"key":"2023020202150858600_btv118-B10","first-page":"1871","article-title":"LIBLINEAR: a library for large linear classification","volume":"9","author":"Fan","year":"2008","journal-title":"J. Mach. Learn. Res."},{"key":"2023020202150858600_btv118-B11","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1186\/1471-2105-12-449","article-title":"ReCount: a multi-experiment resource of analysis-ready RNA-seq gene count datasets","volume":"12","author":"Frazee","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2023020202150858600_btv118-B12","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":"2023020202150858600_btv118-B13","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1093\/bioinformatics\/btr288","article-title":"The role of indirect connections in gene networks in predicting function","volume":"27","author":"Gillis","year":"2011","journal-title":"Bioinformatics"},{"key":"2023020202150858600_btv118-B14","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1093\/bioinformatics\/btq643","article-title":"RSEQtools: a modular framework to analyze RNA-Seq data using compact, anonymized data summaries","volume":"27","author":"Habegger","year":"2011","journal-title":"Bioinformatics"},{"key":"2023020202150858600_btv118-B15","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1101\/gr.135350.111","article-title":"GENCODE: the reference human genome annotation for The ENCODE Project","volume":"22","author":"Harrow","year":"2012","journal-title":"Genome Res."},{"key":"2023020202150858600_btv118-B16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/gbb.12007","article-title":"Genes, behavior and next-generation RNA sequencing","volume":"12","author":"Hitzemann","year":"2013","journal-title":"Genes Brain Behav."},{"key":"2023020202150858600_btv118-B17","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1093\/bioinformatics\/bts245","article-title":"Utilizing RNA-Seq data for de novo coexpression network inference","volume":"28","author":"Iancu","year":"2012","journal-title":"Bioinformatics"},{"key":"2023020202150858600_btv118-B18","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2023020202150858600_btv118-B19","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"2023020202150858600_btv118-B20","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1101\/gr.1910904","article-title":"Coexpression analysis of human genes across many microarray data sets","volume":"14","author":"Lee","year":"2004","journal-title":"Genome Res."},{"key":"2023020202150858600_btv118-B21","doi-asserted-by":"crossref","first-page":"D19","DOI":"10.1093\/nar\/gkq1019","article-title":"The sequence read archive","volume":"39","author":"Leinonen","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2023020202150858600_btv118-B22","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2023020202150858600_btv118-B23","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1038\/nbt.3000","article-title":"Detecting and correcting systematic variation in large-scale RNA sequencing data","volume":"32","author":"Li","year":"2014","journal-title":"Nat. Biotech."},{"key":"2023020202150858600_btv118-B24","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1093\/bioinformatics\/btt688","article-title":"RNA-seq differential expression studies: more sequence or more replication?","volume":"30","author":"Liu","year":"2014","journal-title":"Bioinformatics"},{"key":"2023020202150858600_btv118-B25","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1186\/1471-2105-7-S1-S7","article-title":"ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context","volume":"7","author":"Margolin","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2023020202150858600_btv118-B26","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/nmeth.1226","article-title":"Mapping and quantifying mammalian transcriptomes by RNA-Seq","volume":"5","author":"Mortazavi","year":"2008","journal-title":"Nat. Methods"},{"key":"2023020202150858600_btv118-B27","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1186\/gb-2008-9-s1-s4","article-title":"GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function","volume":"9","author":"Mostafavi","year":"2008","journal-title":"Genome Biol."},{"key":"2023020202150858600_btv118-B28","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1137\/S003614450342480","article-title":"The structure and function of complex networks","volume":"45","author":"Newman","year":"2003","journal-title":"SIAM Rev."},{"key":"2023020202150858600_btv118-B29","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/35001165","article-title":"Proteomics: guilt-by-association goes global","volume":"403","author":"Oliver","year":"2000","journal-title":"Nature"},{"key":"2023020202150858600_btv118-B30","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.cell.2013.10.031","article-title":"Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism","volume":"155","author":"Parikshak","year":"2013","journal-title":"Cell"},{"key":"2023020202150858600_btv118-B31","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":"2023020202150858600_btv118-B32","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1109\/TPAMI.2005.159","article-title":"Feature selection based on mutual information criteria of max-dependency, max-relevance, and min-redundancy","volume":"27","author":"Peng","year":"2005","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell."},{"key":"2023020202150858600_btv118-B33","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1093\/bioinformatics\/btr274","article-title":"parmigene\u2014a parallel R package for mutual information estimation and gene network reconstruction","volume":"27","author":"Sales","year":"2011","journal-title":"Bioinformatics"},{"key":"2023020202150858600_btv118-B34","doi-asserted-by":"crossref","first-page":"e61005","DOI":"10.1371\/journal.pone.0061005","article-title":"Maize gene atlas developed by RNA sequencing and comparative evaluation of transcriptomes based on RNA sequencing and microarrays","volume":"8","author":"Sekhon","year":"2013","journal-title":"PLoS One"},{"key":"2023020202150858600_btv118-B35","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. Biotech."},{"key":"2023020202150858600_btv118-B36","doi-asserted-by":"crossref","first-page":"Article3","DOI":"10.2202\/1544-6115.1027","article-title":"Linear models and empirical bayes methods for assessing differential expression in microarray experiments","volume":"3","author":"Smyth","year":"2004","journal-title":"Stat. Appl. Genet. Mol. Biol."},{"key":"2023020202150858600_btv118-B37","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nbt.1621","article-title":"Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation","volume":"28","author":"Trapnell","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"2023020202150858600_btv118-B38","doi-asserted-by":"crossref","DOI":"10.1093\/bioinformatics\/btu715","article-title":"Measuring the wisdom of the crowds in network-based gene function inference","author":"Verleyen","year":"2015","journal-title":"Bioinformatics"},{"key":"2023020202150858600_btv118-B39","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":"2023020202150858600_btv118-B40","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1093\/bioinformatics\/btp290","article-title":"A global meta-analysis of microarray expression data to predict unknown gene functions and estimate the literature-data divide","volume":"25","author":"Wren","year":"2009","journal-title":"Bioinformatics"},{"key":"2023020202150858600_btv118-B41","doi-asserted-by":"crossref","DOI":"10.1145\/1015330.1015332","article-title":"Solving large scale linear prediction problems using stochastic gradient descent algorithms","volume-title":"International conference on Machine Learning","author":"Zhang","year":"2004"},{"key":"2023020202150858600_btv118-B42","doi-asserted-by":"crossref","first-page":"1128","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":"2023020202150858600_btv118-B43","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1093\/bioinformatics\/bts430","article-title":"Gemma: a resource for the reuse, sharing and meta-analysis of expression profiling data","volume":"28","author":"Zoubarev","year":"2012","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/13\/2123\/49035092\/bioinformatics_31_13_2123.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/13\/2123\/49035092\/bioinformatics_31_13_2123.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T03:41:50Z","timestamp":1675309310000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/31\/13\/2123\/196230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,28]]},"references-count":43,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2015,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btv118","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2015,7,1]]},"published":{"date-parts":[[2015,2,28]]}}}