Dominating Biological Networks 英文参考文献.docVIP

DominatingBiologicalNetworks TijanaMilenkovic′1,VesnaMemisˇevic′2,AnthonyBonato3,Natasˇa Przˇulj4* 1Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, Indiana, United States of America, 2Department of Computer Science, UniversityofCaliforniaIrvine,Irvine,California,UnitedStatesofAmerica,3DepartmentofMathematics,RyersonUniversity,Toronto,Ontario,Canada,4Departmentof Computing,ImperialCollegeLondon,London,UnitedKingdom Abstract Proteinsareessentialmacromoleculesoflifethatcarry outmostcellularprocesses.Sinceproteinsaggregatetoperform function,andsinceprotein-proteininteraction(PPI)networksmodeltheseaggregations,onewouldexpecttouncovernew biologyfromPPInetworktopology.Hence,usingPPInetworkstopredictproteinfunctionandroleofproteinpathwaysin disease has received attention. A debate remains open about whether network properties of ‘‘biologically central (BC)’’ genes (i.e., their protein products), such as those involved in aging, cancer, infectious diseases, or signaling and drug- targetedpathways,exhibitsometopologicalcentralitycomparedtotherestoftheproteinsinthehumanPPInetwork. To help resolve this debate, we design new network-based approaches and apply them to get new insight into biological functionanddisease.WehypothesizethatBCgeneshaveatopologicallycentral(TC)roleinthehumanPPInetwork.We proposetwodifferentconceptsoftopologicalcentrality.Wedesignanewcentralitymeasuretocapturecomplexwiringsof proteinsinthenetworkthatidentifiesasTCthoseproteinsthatresideindenseextendednetworkneighborhoods.Also,we usethenotionofdominationandfinddominatingsets(DSs)inthePPInetwork,i.e.,setsofproteinssuchthateveryprotein iseitherintheDSorisaneighboroftheDS.Clearly,aDShasaTCrole,asitenablesefficientcommunicationbetween differentnetworkparts. WefindstatisticallysignificantenrichmentinBCgenesofTCnodesandoutperformtheexisting methodsindicatingthatgenesinvolvedinkeybiologicalprocessesoccupytopologicallycomplexanddenseregionsofthe networkandcorrespon