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6/07/16 Weightedgenecoexpressionnetwork analysis(WGCNA)prac;cal Integra;veGenomicsmodule MichaelInouye CentreforSystemsGenomics UniversityofMelbourne,Australia SummerIns@tuteinSta@s@calGene@cs2016 SeaBle,USA @minouye271 inouyelab.org Geneco-expressionnetworks • Weighted,undirected completegenenetwork – Nodes:genes/probes – Edges:|cor(node_i,node_j)|γ • Scale-freeassump@onand[0,1] • Iden;fysubnets(modules/ clusters) – Typicallysubnetsrepresent knownbiologicalpathways – Variousmethodsandtoolsfor clustering 1 6/07/16 Whatwe’redoingtoday • Datamanagementandfiltering • Networkconstruc@on • Moduledetec@on • Moduleassocia@onanalysis GeHngstarted (ifyouhaven’talreadydoneso) 2 6/07/16 3 6/07/16 4 6/07/16 What’sitdoing? • CalculatePearsoncorrela@oncoefficients betweenallpairsofgenes • Useapowertransformtosa@sfyscale-free topologycriteria(selectso]powerthreshold) • Inferanetworkwhere – Nodes:Genes – Edges:Pearsoncorrela@onsraisedtotheselected power 5 6/07/16 What’sitdoing? • Goal:Getthemostcoherentgenesubnetworksaspossible • Insteadofusingthecorrela@on-basededges,WGCNAis calcula@ngadistancemeasurecalledtopologicalsimilarity (TOM): Yip&Horvath,BMCBioinf2007 6 6/07/16 What’sitdoing? • HierarchicalclusteringofTOMmatrix • Movethroughthedendrogramwitha dynamiccufngalgorithm Yip&Horvath,BMCBioinf2007 7 6/07/16 Phenotypeassocia;onanalysis 8 6/07/16 SpecialthankstoScoLRitchie Networkinferenceadaptedfromhisscript 9