{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T12:17:47Z","timestamp":1776860267170,"version":"3.51.2"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2008,8,15]],"date-time":"2008-08-15T00:00:00Z","timestamp":1218758400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1000117","type":"journal-article","created":{"date-parts":[[2008,8,14]],"date-time":"2008-08-14T21:48:21Z","timestamp":1218750501000},"page":"e1000117","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":684,"title":["Geometric Interpretation of Gene Coexpression Network Analysis"],"prefix":"10.1371","volume":"4","author":[{"given":"Steve","family":"Horvath","sequence":"first","affiliation":[]},{"given":"Jun","family":"Dong","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2008,8,15]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1126\/science.1073374","article-title":"Hierarchical organization of modularity in metabolic networks.","volume":"297","author":"E Ravasz","year":"2002","journal-title":"Science"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1093\/bioinformatics\/bth166","article-title":"Defining transcription modules using large-scale gene expression data.","volume":"20","author":"J Ihmels","year":"2004","journal-title":"Bioinformatics"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrg1272","article-title":"Network biology: understanding the cell&apos;s functional organization.","volume":"5","author":"AL Barabasi","year":"2004","journal-title":"Nat Rev Genet"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"4947","DOI":"10.1242\/jcs.02714","article-title":"Scale-free networks in cell biology.","volume":"118","author":"R Albert","year":"2005","journal-title":"J Cell Sci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1126\/science.298.5594.824","article-title":"Network motifs: simple building blocks of complex networks.","volume":"298","author":"R Milo","year":"2002","journal-title":"Science"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.tig.2004.11.010","article-title":"Modular analysis of the transcriptional regulatory network of E. coli.","volume":"21","author":"O Resendis-Antonio","year":"2005","journal-title":"Trends Genet"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"7841","DOI":"10.1073\/pnas.0500365102","article-title":"Topological units of environmental signal processing in the transcriptional regulatory network of Escherichia coli.","volume":"102","author":"G Balazsi","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1752-0509-1-24","article-title":"Understanding network concepts in modules.","volume":"1","author":"J Dong","year":"2007","journal-title":"BMC Syst Biol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/30918","article-title":"Collective dynamics of \u2018small-world\u2019 networks.","volume":"393","author":"DJ Watts","year":"1998","journal-title":"Nature"},{"key":"ref10","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":"M Eisen","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"S233","DOI":"10.1093\/bioinformatics\/18.suppl_1.S233","article-title":"Discovering regulatory and signalling circuits in molecular interaction networks.","volume":"18","author":"T Ideker","year":"2002","journal-title":"Bioinformatics"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"i222","DOI":"10.1093\/bioinformatics\/btm222","article-title":"Systematic discovery of functional modules and context-specific functional annotation of human genome.","volume":"23","author":"Y Huang","year":"2007","journal-title":"Bioinformatics"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"12182","DOI":"10.1073\/pnas.220392197","article-title":"Discovering functional relationships between RNA expression and chemotherapeutic susceptibility using relevance networks.","volume":"97","author":"A Butte","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"12783","DOI":"10.1073\/pnas.192159399","article-title":"Transitive functional annotation by shortest path analysis of gene expression data.","volume":"99","author":"X Zhou","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/1471-2105-3-34","article-title":"Automated modelling of signal transduction networks.","volume":"3","author":"M Steffen","year":"2002","journal-title":"BMC Bioinformatics"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1126\/science.1087447","article-title":"A gene-coexpression network for global discovery of conserved genetic modules.","volume":"302","author":"JM Stuart","year":"2003","journal-title":"Science"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1093\/bioinformatics\/bth234","article-title":"Gene co-expression network topology provides a framework for molecular characterization of cellular state.","volume":"20","author":"S Carter","year":"2004","journal-title":"Bioinformatics"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1371\/journal.pbio.0020009","article-title":"Similarities and differences in genome-wide expression data of six organisms.","volume":"2","author":"S Bergmann","year":"2004","journal-title":"PLoS Biol"},{"key":"ref19","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":"B Zhang","year":"2005","journal-title":"Stat Appl Genet Mol Biol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1093\/bioinformatics\/bti440","article-title":"Differential network expression during drug and stress response.","volume":"21","author":"L Cabusora","year":"2005","journal-title":"Bioinformatics"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1104\/pp.106.080358","article-title":"Transcriptional coordination of the metabolic network in arabidopsis.","volume":"142","author":"H Wei","year":"2006","journal-title":"Plant Physiol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"e89","DOI":"10.1371\/journal.pcbi.0020089","article-title":"Extracting gene networks for low-dose radiation using graph theoretical algorithms.","volume":"2","author":"BH Voy","year":"2006","journal-title":"PLoS Comput Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1371\/journal.pgen.0020130","article-title":"Integrating genetics and network analysis to characterize genes related to mouse weight.","volume":"2","author":"A Ghazalpour","year":"2006","journal-title":"PloS Genet"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"17402","DOI":"10.1073\/pnas.0608396103","article-title":"Analysis of oncogenic signaling networks in glioblastoma identifies aspm as a novel molecular target.","volume":"103","author":"S Horvath","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"17973","DOI":"10.1073\/pnas.0605938103","article-title":"Conservation and evolution of gene coexpression networks in human and chimpanzee brains.","volume":"103","author":"M Oldham","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s00335-007-9043-3","article-title":"Weighted gene coexpression network analysis strategies applied to mouse weight.","volume":"18","author":"T Fuller","year":"2007","journal-title":"Mamm Genome"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1093\/bioinformatics\/btl442","article-title":"Eigengene-based linear discriminant model for tumor classification using gene expression microarray data.","volume":"22","author":"R Shen","year":"2006","journal-title":"Bioinformatics"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/msb4100180","article-title":"Network-based classification of breast cancer metastasis.","volume":"3","author":"H Chuang","year":"2007","journal-title":"Mol Syst Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/35019019","article-title":"Error and attack tolerance of complex networks.","volume":"406","author":"R Albert","year":"2000","journal-title":"Nature"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/35075138","article-title":"Lethality and centrality in protein networks.","volume":"411","author":"H Jeong","year":"2001","journal-title":"Nature"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1103\/RevModPhys.74.47","article-title":"Statistical mechanics of complex networks.","volume":"74","author":"R Albert","year":"2002","journal-title":"Rev Mod Phys"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nature02555","article-title":"Evidence for dynamically organized modularity in the yeast protein\u2013protein interaction network.","volume":"430","author":"J Han","year":"2004","journal-title":"Nature"},{"key":"ref33","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":"M Carlson","year":"2006","journal-title":"BMC Genomics"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/nature02289","article-title":"Global organization of metabolic fluxes in the bacterium Escherichia coli.","volume":"427","author":"E Almaas","year":"2004","journal-title":"Nature"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/0378-8733(81)90014-9","article-title":"The degree variance: an index of graph heterogeneity.","volume":"3","author":"T Snijders","year":"1981","journal-title":"Soc Networks"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0378-8733(78)90021-7","article-title":"Centrality in social networks: conceptual clarification.","volume":"1","author":"L Freeman","year":"1978","journal-title":"Soc Networks"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/1471-2105-5-199","article-title":"Hierarchical structure and modules in the Escherichia coli transcriptional regulatory network revealed by a new top-down approach.","volume":"5","author":"H Ma","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"5766","DOI":"10.1073\/pnas.082090499","article-title":"A simple model of global cascades on random networks.","volume":"99","author":"DJ Watts","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"12741","DOI":"10.1073\/pnas.0605457103","article-title":"Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipids.","volume":"103","author":"P Gargalovic","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1093\/bioinformatics\/btm563","article-title":"Defining clusters from a hierarchical cluster tree: the Dynamic Tree Cut library for R.","volume":"24","author":"P Langfelder","year":"2007","journal-title":"Bioinformatics"},{"key":"ref41","first-page":"343","article-title":"Comparative analysis of protein domain organization.","volume":"14","author":"Y Ye","year":"2004","journal-title":"Genome Biol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1471-2105-8-22","article-title":"Gene network interconnectedness and the generalized topological overlap measure.","volume":"8","author":"A Yip","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1093\/bioinformatics\/btl581","article-title":"Network neighborhood analysis with the multi-node topological overlap measure.","volume":"23","author":"A Li","year":"2007","journal-title":"Bioinformatics"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"10101","DOI":"10.1073\/pnas.97.18.10101","article-title":"Singular value decomposition for genome-wide expression data processing and modelling.","volume":"97","author":"O Alter","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"8409","DOI":"10.1073\/pnas.150242097","article-title":"Fundamental patterns underlying gene expression profiles: simplicity from complexity.","volume":"97","author":"N Holter","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"11462","DOI":"10.1073\/pnas.201162998","article-title":"Predicting the clinical status of human breast cancer by using gene expression profiles.","volume":"98","author":"M West","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"6567","DOI":"10.1073\/pnas.082099299","article-title":"Diagnosis of multiple cancer types by shrunken centroids of gene expression.","volume":"99","author":"R Tibshirani","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"6163","DOI":"10.1073\/pnas.092576199","article-title":"Reverse engineering gene networks using singular value decomposition and robust regression.","volume":"99","author":"MS Yeung","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"15522","DOI":"10.1073\/pnas.2136632100","article-title":"Network component analysis: reconstruction of regulatory signals in biological systems.","volume":"100","author":"J Liao","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.jmva.2004.02.009","article-title":"Sparse graphical models for exploring gene expression data.","volume":"90","author":"D Adrian","year":"2004","journal-title":"J Multivar Anal"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"5959","DOI":"10.1073\/pnas.0701068104","article-title":"Metagene projection for cross-platform, cross-species characterization of global transcriptional states.","volume":"104","author":"P Tamayo","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/1752-0509-1-54","article-title":"Eigengene networks for studying the relationships between co-expression modules.","volume":"1","author":"P Langfelder","year":"2007","journal-title":"BMC Syst Biol"},{"key":"ref53","first-page":"1","article-title":"On the \u2018probable error\u2019 of a coefficient of correlation deduced from a small sample.","volume":"1","author":"RA Fisher","year":"1915","journal-title":"Metron"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.1091\/mbc.9.12.3273","article-title":"Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization.","volume":"9","author":"PT Spellman","year":"1998","journal-title":"Mol Biol Cell"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1093\/bioinformatics\/16.8.707","article-title":"Genetic network inference: from co-expression clustering to reverse engineering.","volume":"16","author":"P D'haeseleer","year":"2000","journal-title":"Bioinformatics"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"e51","DOI":"10.1371\/journal.pcbi.0020051","article-title":"Reverse engineering the gap gene network of Drosophila melanogaster.","volume":"2","author":"TJ Perkins","year":"2005","journal-title":"PLoS Comput Biol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"e52","DOI":"10.1371\/journal.pcbi.0020052","article-title":"Iterative reconstruction of transcriptional regulatory networks: an algorithmic approach.","volume":"2","author":"CL Barrett","year":"2006","journal-title":"PLoS Comput Biol"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"e161","DOI":"10.1371\/journal.pcbi.0020161","article-title":"Computational inference of neural information flow networks.","volume":"2","author":"VA Smith","year":"2006","journal-title":"PLoS Comput Biol"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.1371\/journal.pcbi.0030109","article-title":"Modeling systems-level regulation of host immune responses.","volume":"3","author":"J Thakar","year":"2007","journal-title":"PLoS Comput Biol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"e175","DOI":"10.1371\/journal.pcbi.0030175","article-title":"Orthologous transcription factors in bacteria have different functions and regulate different genes.","volume":"3","author":"MN Price","year":"2007","journal-title":"PLoS Comput Biol"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"e129","DOI":"10.1371\/journal.pcbi.0030129","article-title":"A primer on learning in Bayesian networks for computational biology.","volume":"3","author":"C Needham","year":"2007","journal-title":"PLoS Comput Biol"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T10:47:04Z","timestamp":1557744424000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000117"}},"subtitle":[],"editor":[{"given":"Satoru","family":"Miyano","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2008,8,15]]},"references-count":61,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2008,8,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000117","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8,15]]}}}