Dynamic Changes in Protein Functional Linkage Networks Revealed by Integration with Gene Expression Data 英文参考文献.docVIP

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Dynamic Changes in Protein Functional Linkage Networks Revealed by Integration with Gene Expression Data 英文参考文献.doc

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Dynamic Changes in Protein Functional Linkage Networks Revealed by Integration with Gene Expression Data 英文参考文献

DynamicChangesinProteinFunctionalLinkage NetworksRevealedbyIntegrationwithGeneExpression Data ShubhadaR.Hegde,PalanisamyManimaran,ShekharC.Mande* CentreforDNAFingerprintingandDiagnostics,Nacharam,Hyderabad,India Abstract Responseofcellstochangingenvironmentalconditionsisgovernedbythedynamicsofintricatebiomolecularinteractions. Itmaybereasonabletoassume,proteinsbeingthedominantmacromoleculesthatcarryoutroutinecellularfunctions,that understandingthedynamicsofprotein:proteininteractionsmightyieldusefulinsightsintothecellularresponses.Thelarge- scaleproteininteractiondatasetsare,however,unabletocapturethechangesintheprofileofprotein:proteininteractions. Inordertounderstandhowtheseinteractionschangedynamically,wehaveconstructedconditionalproteinlinkagesfor Escherichia coli by integrating functional linkages and gene expression information. As a case study, we have chosen to analyzeUVexposureinwild-typeandSOSdeficientE.coliat20minutespostirradiation.Theconditionalnetworksexhibit similar topological properties. Although the global topological properties of the networks are similar, many subtle local changesareobserved,whicharesuggestiveofthecellularresponsetotheperturbations.Somesuchchangescorrespond todifferencesinthepathlengthsamongthenodesofcarbohydratemetabolismcorrelatingwithitslossinefficiencyinthe UV treated cells. Similarly, expression of hubs under unique conditions reflects the importance of these genes. Various centralitymeasuresappliedtothenetworksindicateincreasedimportanceforreplication,repair,andotherstressproteins forthecellsunderUVtreatment,asanticipated.Wethusproposeanovelapproachforstudyinganorganismatthesystems levelbyintegratinggenome-widefunctionallinkagesandthegeneexpressiondata. Citation:HegdeSR,ManimaranP,MandeSC(2008)DynamicChangesinProteinFunctionalLinkageNetworksRevealedbyIntegrationwithGeneExpression Data.PLoSComputBiol4(11):e1000237.doi:10.1371/journal.pcbi.1000237 Editor:LuhuaLai,PekingUniversity,China ReceivedMay8,2008;AcceptedOctober20,20