Simultaneous Clustering of Multiple Gene Expression and Physical Interaction Datasets 英文参考文献.docVIP

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Simultaneous Clustering of Multiple Gene Expression and Physical Interaction Datasets 英文参考文献.doc

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Simultaneous Clustering of Multiple Gene Expression and Physical Interaction Datasets 英文参考文献

SimultaneousClusteringofMultipleGeneExpression andPhysicalInteractionDatasets ManikandanNarayanan1*¤a,AdrianVetta2,EricE.Schadt1¤b,JunZhu1*¤c 1Department of Genetics, Rosetta Inpharmatics (Merck), Seattle, Washington, United States of America, 2Department of Mathematics and Statistics, and School of ComputerScience,McGillUniversity,Montreal,Quebec,Canada Abstract Manygenome-widedatasetsareroutinelygeneratedtostudydifferentaspectsofbiologicalsystems,butintegratingthem toobtainacoherentviewoftheunderlyingbiologyremainsachallenge.Weproposesimultaneousclusteringofmultiple networksasaframeworktointegratelarge-scaledatasetsontheinteractionsamongandactivitiesofcellularcomponents. Specifically,wedevelopanalgorithmJointClusterthatfindssetsofgenesthatclusterwellinmultiplenetworksofinterest, such as coexpression networks summarizing correlations among the expression profiles of genes and physical networks describing protein-protein and protein-DNA interactions among genes or gene-products. Our algorithm provides an efficientsolutiontoawell-definedproblemofjointlyclusteringnetworks,usingtechniquesthatpermitcertaintheoretical guaranteesonthequalityofthedetectedclusteringrelativetotheoptimalclustering.Theseguaranteescoupledwithan effectivescalingheuristicandtheflexibilitytohandlemultipleheterogeneousnetworksmakeourmethodJointClusteran advance over earlier approaches. Simulation results showed JointCluster to be more robust than alternate methods in recoveringclustersimplantedinnetworkswithhighfalsepositiverates.InsystematicevaluationofJointClusterandsome earlierapproachesforcombinedanalysisoftheyeastphysicalnetworkandtwogeneexpressiondatasetsunderglucose and ethanol growth conditions, JointCluster discovers clusters that are more consistently enriched for various reference classescapturingdifferentaspectsofyeastbiologyoryieldbettercoverageoftheanalysedgenes.Theserobustclusters, whicharesupportedacrossmultiplegenomicdatasetsanddiversereferenceclasses,agreewithknownbiologyofyeast