Analysis of Combinatorial Regulation Scaling of Partnerships between Regulators with the Number of Governed Targets 英文参考文献.docVIP

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Analysis of Combinatorial Regulation Scaling of Partnerships between Regulators with the Number of Governed Targets 英文参考文献.doc

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Analysis of Combinatorial Regulation Scaling of Partnerships between Regulators with the Number of Governed Targets 英文参考文献

AnalysisofCombinatorialRegulation:Scalingof PartnershipsbetweenRegulatorswiththeNumberof GovernedTargets NitinBhardwaj1,MatthewB.Carson2,AlexejAbyzov1,Koon-KiuYan1,HuiLu2,MarkB.Gerstein1,3,4* 1PrograminComputationalBiologyandBioinformatics,YaleUniversity,NewHaven,Connecticut,UnitedStatesofAmerica,2BioinformaticsProgram,UniversityofIllinois atChicago,Chicago,Illinois,UnitedStatesofAmerica,3DepartmentofMolecularBiophysicsandBiochemistry,YaleUniversity,NewHaven,Connecticut,UnitedStatesof America,4DepartmentofComputerScience,YaleUniversity,NewHaven,Connecticut,UnitedStatesofAmerica Abstract Throughcombinatorialregulation,regulatorspartnerwitheachothertocontrolcommontargetsandthisallowsasmall number of regulators to govern manytargets. One interesting question is that given this combinatorial regulation, how doesthenumberofregulatorsscalewiththenumberoftargets?Here,weaddressthisquestionbybuildingandanalyzing co-regulation(co-transcriptionandco-phosphorylation)networksthatdescribepartnershipsbetweenregulatorscontrolling commongenes.Wecarryoutanalysesacrossfivediversespecies:Escherichiacolitohuman.Theserevealmanypropertiesof partnershipnetworks,suchastheabsenceofaclassicalpower-lawdegreedistributiondespitetheexistenceofnodeswith many partners. We also find that the number of co-regulatory partnerships follows an exponential saturation curve in relationtothenumberoftargets.(ForE.coliandBacillussubtilis,onlythebeginninglinearpartofthiscurveisevidentdue toarrangementofgenesintooperons.)Togainintuitionintothesaturationprocess,werelatethebiologicalregulationto morecommonplacesocialcontextswhereasmallnumberofindividualscanformanintricatewebofconnectionsonthe internet.Indeed,wefindthatthesizeofpartnershipnetworkssaturatesevenasthecomplexityoftheiroutputincreases. Wealsopresentavarietyofmodelstoaccountforthesaturationphenomenon.Inparticular,wedevelopasimpleanalytical modeltoshowhownewpartnershipsareacquiredwithanincreasingnumberoftargetgenes;withcertainassumptions,it reproducest