{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T16:36:47Z","timestamp":1768322207076,"version":"3.49.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Microarray-based gene expression studies have great potential but are frequently difficult to interpret due to their overwhelming dimensions. Recent studies have shown that the analysis of expression data can be improved by its integration with protein interaction networks, but the performance of these analyses has been hampered by the uneven quality of the interaction data.<\/jats:p>\n               <jats:p>Results: We present Co-Expression Zone ANalysis using NEtworks (CEZANNE), a novel confidence-based method for extraction of functionally coherent co-expressed gene sets. CEZANNE uses probabilities for individual interactions, which can be computed by any available method. We propose a probabilistic model and a weighting scheme in which the likelihood of the connectivity of a subnetwork is related to the weight of its minimum cut. Applying CEZANNE to an expression dataset of DNA damage response in Saccharomyces cerevisiae, we recover both known and novel modules and predict novel protein functions. We show that CEZANNE outperforms previous methods for analysis of expression and interaction data.<\/jats:p>\n               <jats:p>Availability: CEZANNE is available as part of the MATISSE software at http:\/\/acgt.cs.tau.ac.il\/matisse.<\/jats:p>\n               <jats:p>Contact: \u00a0rshamir@tau.ac.il<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btp118","type":"journal-article","created":{"date-parts":[[2009,3,19]],"date-time":"2009-03-19T00:24:17Z","timestamp":1237422257000},"page":"1158-1164","source":"Crossref","is-referenced-by-count":94,"title":["Identifying functional modules using expression profiles and confidence-scored protein interactions"],"prefix":"10.1093","volume":"25","author":[{"given":"Igor","family":"Ulitsky","sequence":"first","affiliation":[{"name":"Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel"}]},{"given":"Ron","family":"Shamir","sequence":"additional","affiliation":[{"name":"Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel"}]}],"member":"286","published-online":{"date-parts":[[2009,3,17]]},"reference":[{"key":"2023013110282188100_B1","doi-asserted-by":"crossref","first-page":"2006 0001","DOI":"10.1038\/msb4100043","article-title":"Global analysis of gene function in yeast by quantitative phenotypic profiling","volume":"2","author":"Brown","year":"2006","journal-title":"Mol. Syst. Biol."},{"key":"2023013110282188100_B2","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":"Cabusora","year":"2005","journal-title":"Bioinformatics"},{"key":"2023013110282188100_B3","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/msb4100180","article-title":"Network-based classification of breast cancer metastasis","volume":"3","author":"Chuang","year":"2007","journal-title":"Mol. Syst. Biol."},{"key":"2023013110282188100_B4","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1074\/mcp.M600381-MCP200","article-title":"Toward a comprehensive atlas of the physical interactome of Saccharomyces cerevisiae","volume":"6","author":"Collins","year":"2007","journal-title":"Mol. Cell Proteomics"},{"key":"2023013110282188100_B5","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1042\/bj20020429","article-title":"Calmodulin controls organization of the actin cyto-skeleton via regulation of phosphatidylinositol (4,5)-bisphosphate synthesis in Saccharomyces cerevisiae","volume":"366","author":"Desrivieres","year":"2002","journal-title":"Biochem. J"},{"key":"2023013110282188100_B6","doi-asserted-by":"crossref","first-page":"5203","DOI":"10.1046\/j.1432-1033.2002.03226.x","article-title":"Tag-mediated isolation of yeast mitochondrial ribosome and mass spectrometric identification of its new components","volume":"269","author":"Gan","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"2023013110282188100_B7","doi-asserted-by":"crossref","first-page":"4241","DOI":"10.1091\/mbc.11.12.4241","article-title":"Genomic expression programs in the response of yeast cells to environmental changes","volume":"11","author":"Gasch","year":"2000","journal-title":"Mol. Biol. Cell"},{"key":"2023013110282188100_B8","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1091\/mbc.12.10.2987","article-title":"Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p","volume":"12","author":"Gasch","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"2023013110282188100_B9","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1093\/bioinformatics\/btm294","article-title":"Edge-based scoring and searching method for identifying condition-responsive protein-protein interaction sub-network","volume":"23","author":"Guo","year":"2007","journal-title":"Bioinformatics"},{"issue":"Suppl 1","key":"2023013110282188100_B10","doi-asserted-by":"crossref","first-page":"S145","DOI":"10.1093\/bioinformatics\/18.suppl_1.S145","article-title":"Co-clustering of biological networks and gene expression data","volume":"18","author":"Hanisch","year":"2002","journal-title":"Bioinformatics"},{"key":"2023013110282188100_B11","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/nature02026","article-title":"Global analysis of protein localization in budding yeast","volume":"425","author":"Huh","year":"2003","journal-title":"Nature"},{"issue":"Suppl 1","key":"2023013110282188100_B12","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":"Ideker","year":"2002","journal-title":"Bioinformatics"},{"key":"2023013110282188100_B13","doi-asserted-by":"crossref","first-page":"8157","DOI":"10.1128\/MCB.20.21.8157-8167.2000","article-title":"Regulatory networks revealed by transcriptional profiling of damaged Saccharomyces cerevisiae cells: Rpn4 links base excision repair with proteasomes","volume":"20","author":"Jelinsky","year":"2000","journal-title":"Mol. Cell Biol."},{"key":"2023013110282188100_B14","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1126\/science.1075090","article-title":"Transcriptional regulatory networks in Saccharomyces cerevisiae","volume":"298","author":"Lee","year":"2002","journal-title":"Science"},{"key":"2023013110282188100_B15","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1093\/bioinformatics\/btn081","article-title":"Network-constrained regularization and variable selection for analysis of genomic data","volume":"24","author":"Li","year":"2008","journal-title":"Bioinformatics"},{"key":"2023013110282188100_B16","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1074\/mcp.M700287-MCP200","article-title":"PRINCESS, a protein interaction confidence evaluation system with multiple data sources","volume":"7","author":"Li","year":"2008","journal-title":"Mol. Cell Proteomics"},{"key":"2023013110282188100_B17","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1371\/journal.pgen.0030096","article-title":"Network-based analysis of affected biological processes in type 2 diabetes models","volume":"3","author":"Liu","year":"2007","journal-title":"PLoS Genet"},{"key":"2023013110282188100_B18","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.febslet.2004.04.078","article-title":"Regulatory mechanisms controlling biogenesis of ubiquitin and the proteasome","volume":"567","author":"London","year":"2004","journal-title":"FEBS Lett"},{"key":"2023013110282188100_B19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/bioinformatics\/btl569","article-title":"CGI: a new approach for prioritizing genes by combining gene expression and protein-protein interaction data","volume":"23","author":"Ma","year":"2007","journal-title":"Bioinformatics"},{"key":"2023013110282188100_B20","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/1471-2164-6-141","article-title":"The stress response against denatured proteins in the deletion of cytosolic chaperones SSA1\/2 is different from heat-shock response in Saccharomyces cerevisiae","volume":"6","author":"Matsumoto","year":"2005","journal-title":"BMC Genomics"},{"key":"2023013110282188100_B21","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nature07213","article-title":"Regulatory networks define phenotypic classes of human stem cell lines","volume":"455","author":"M\u00fcller","year":"2008","journal-title":"Nature"},{"key":"2023013110282188100_B22","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1093\/bioinformatics\/btm019","article-title":"Gene expression network analysis and applications to immunology","volume":"23","author":"Nacu","year":"2007","journal-title":"Bioinformatics"},{"key":"2023013110282188100_B23","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.cell.2006.06.040","article-title":"Exploring the mode-of-action of bioactive compounds by chemical-genetic profiling in yeast","volume":"126","author":"Parsons","year":"2006","journal-title":"Cell"},{"key":"2023013110282188100_B24","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1093\/bioinformatics\/bti069","article-title":"Inferring pathways from gene lists using a literature-derived network of biological relationships","volume":"21","author":"Rajagopalan","year":"2005","journal-title":"Bioinformatics"},{"key":"2023013110282188100_B25","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1471-2105-8-35","article-title":"Classification of microarray data using gene networks","volume":"8","author":"Rapaport","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"2023013110282188100_B26","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1038\/nbt1103","article-title":"Probabilistic model of the human protein-protein interaction network","volume":"23","author":"Rhodes","year":"2005","journal-title":"Nat. Biotechnol."},{"issue":"Suppl 1","key":"2023013110282188100_B27","doi-asserted-by":"crossref","first-page":"i264","DOI":"10.1093\/bioinformatics\/btg1037","article-title":"Discovering molecular pathways from protein interaction and gene expression data","volume":"19","author":"Segal","year":"2003","journal-title":"Bioinformatics"},{"key":"2023013110282188100_B28","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1186\/1471-2105-6-232","article-title":"EXPANDER\u2013an integrative program suite for microarray data analysis","volume":"6","author":"Shamir","year":"2005","journal-title":"BMC Bioinformatics"},{"key":"2023013110282188100_B29","first-page":"307","article-title":"CLICK: a clustering algorithm with applications to gene expression analysis","volume":"8","author":"Sharan","year":"2000","journal-title":"Proc. Int. Conf. Intell. Syst. Mol. Biol."},{"key":"2023013110282188100_B30","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/ng929","article-title":"Systematic screen for human disease genes in yeast","volume":"31","author":"Steinmetz","year":"2002","journal-title":"Nat. Genet."},{"key":"2023013110282188100_B31","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1145\/263867.263872","article-title":"A simple min-cut algorithm","volume":"44","author":"Stoer","year":"1997","journal-title":"JACM"},{"key":"2023013110282188100_B32","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1186\/1471-2105-7-360","article-title":"A direct comparison of protein interaction confidence assignment schemes","volume":"7","author":"Suthram","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2023013110282188100_B33","doi-asserted-by":"crossref","first-page":"2005 0002","DOI":"10.1038\/msb4100005","article-title":"Integrative analysis of genome-wide experiments in the context of a large high-throughput data compendium","volume":"1","author":"Tanay","year":"2005","journal-title":"Mol. Syst. Biol."},{"key":"2023013110282188100_B34","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s00493-007-0045-2","article-title":"Fully-dynamic min-cut","volume":"27","author":"Thorup","year":"2007","journal-title":"Combinatorica"},{"key":"2023013110282188100_B35","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1752-0509-1-8","article-title":"Identification of functional modules using network topology and high-throughput data","volume":"1","author":"Ulitsky","year":"2007","journal-title":"BMC Syst. Biol"},{"key":"2023013110282188100_B36","first-page":"347","article-title":"Detecting Disease-specific Dysregulated Pathways via Analysis of Clinical Expression Profiles","volume-title":"Proceedings of Research in Computational Molecular Biology (RECOMB) 2008.","author":"Ulitsky","year":"2008"},{"key":"2023013110282188100_B37","volume-title":"Information Retrieval.","author":"Van Rijsbergen","year":"1979"},{"key":"2023013110282188100_B38","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nature750","article-title":"Comparative assessment of large-scale data sets of protein-protein interactions","volume":"417","author":"von Mering","year":"2002","journal-title":"Nature"},{"key":"2023013110282188100_B39","doi-asserted-by":"crossref","first-page":"D358","DOI":"10.1093\/nar\/gkl825","article-title":"STRING 7\u2013recent developments in the integration and prediction of protein interactions","volume":"35","author":"von Mering","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"2023013110282188100_B40","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nature06107","article-title":"Natural history and evolutionary principles of gene duplication in fungi","volume":"449","author":"Wapinski","year":"2007","journal-title":"Nature"},{"key":"2023013110282188100_B41","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/bioinformatics\/btm612","article-title":"Incorporating gene networks into statistical tests for genomic data via a spatially correlated mixture model","volume":"24","author":"Wei","year":"2008","journal-title":"Bioinformatics"},{"key":"2023013110282188100_B42","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1093\/nar\/gkl219","article-title":"Prediction of yeast protein-protein interaction network: insights from the Gene Ontology and annotations","volume":"34","author":"Wu","year":"2006","journal-title":"Nucleic Acids Res"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/25\/9\/1158\/48984987\/bioinformatics_25_9_1158.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/25\/9\/1158\/48984987\/bioinformatics_25_9_1158.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T20:34:52Z","timestamp":1675197292000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/25\/9\/1158\/203927"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3,17]]},"references-count":42,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2009,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btp118","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,5,1]]},"published":{"date-parts":[[2009,3,17]]}}}