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1、LeadingEdgePerspectivePrinciplesandStrategiesforDevelopingNetworkModelsinCancerDanaPeer1,2,*andNirHacohen3,4,51DepartmentofBiologicalSciences,ColumbiaUniversity,1212AmsterdamAvenue,NewYork,NY10027,USA2CenterforComputationalBiologyandBioinformatics,ColumbiaUniversity,1130St.Nich
2、olasAvenue,NewYork,NY10032,USA3BroadInstituteofMITandHarvard,7CambridgeCenter,Cambridge,MA02142,USA4CenterforImmunologyandInflammatoryDiseases,MassachusettsGeneralHospital,14913thStreet,Charlestown,MA02129,USA5DepartmentofMedicine,HarvardMedicalSchool,Boston,MA02115,USA*Correspo
3、ndence:dpeer@biology.columbia.eduDOI10.1016/j.cell.2011.03.001Thefloodofgenome-widedatageneratedbyhigh-throughputtechnologiescurrentlyprovidesbiol-ogistswithanunprecedentedopportunity:tomanipulate,query,andreconstructfunctionalmolec-ularnetworksofcells.Here,weoutlinethreeunderly
4、ingprinciplesandsixstrategiestoinfernetworkmodelsfromgenomicdata.Then,usingcancerasanexample,wedescribeexperimentalandcomputationalapproachestoinferdifferentialnetworksthatcanidentifygenesandprocessesdrivingdiseasephenotypes.Inconclusion,wediscusshowanetwork-levelunder-standing
5、ofcancercanbeusedtopredictdrugresponseandguidetherapeutics.CellscontainavastarrayofmolecularstructuresthatcomeSuchaglobalunderstandingofnetworkscanhavetransforma-togethertoformcomplex,dynamic,andplasticnetworks.Thetivevalue,allowingbiologiststodissectoutthepathwaysthatrecentdev
6、elopmentofhigh-throughput,massivelyparalleltech-goawryindiseaseandthenidentifyoptimaltherapeuticstrate-nologieshasprovidedbiologistswithanextensive,althoughstillgiesforcontrollingthem.incomplete,listofthesecellularparts.TheemergingchallengeToillustratethepotentialimpactofglobal
7、models,wenoteoverthenextdecadeistosystematicallyassemblethesethattheeffectofacancerdrugisoftenhardtopredictbecausecomponentsintofunctionalmolecularandcellularnetworkscrosstalkandfeedbackarestillpoorlymappedinmostandthentousethesenetworkstoanswerfundamentalques-signalingpathways
8、.Forexample,themammaliantargetoftionsaboutcellularproc
