Scalable Steady State Analysis of Boolean Biological Regulatory Networks 英文参考文献.docVIP

ScalableSteadyStateAnalysisofBooleanBiological RegulatoryNetworks FerhatAy*,FeiXu,TamerKahveci ComputerandInformationScienceandEngineering,UniversityofFlorida,Gainesville,Florida,UnitedStatesofAmerica Abstract Background: Computing the long term behavior of regulatory and signaling networks is critical in understanding how biological functions take place in organisms. Steady states of these networks determine the activity levels of individual entities in the long run. Identifying all the steady states of these networks is difficult due to the state space explosion problem. Methodology:Inthispaper,weproposeamethodforidentifyingallthesteadystatesofBooleanregulatoryandsignaling networksaccuratelyandefficiently.Webuildamathematicalmodelthatallowspruningalargeportionofthestatespace quicklywithoutcausinganyfalsedismissals.Fortheremainingstatespace,whichistypicallyverysmallcomparedtothe wholestatespace,wedeveloparandomizedtraversalmethodthatextractsthesteadystates.Weestimatethenumberof steadystates,andtheexpectedbehaviorofindividualgenesandgenepairsinsteadystatesinanonlinefashion.Also,we formulateastoppingcriterionthatterminatesthetraversalassoonasusersuppliedpercentageoftheresultsarereturned withhighconfidence. Conclusions: This method identifies the observed steady states of boolean biological networks computationally. Our algorithm successfully reported the G1 phases of both budding and fission yeast cell cycles. Besides, the experi- mentssuggestthatthismethodisusefulinidentifyingco-expressedgenesaswell.Byanalyzingthesteadystateprofile of Hedgehog network, we were able to find the highly co-expressed gene pair GL1-SMO together with other such pairs. Availability:Sourcecodeofthisworkisavailableat/palSteady.htmltwocolumnfalse] Citation: AyF, Xu F,Kahveci T(2009) ScalableSteady State Analysis ofBoolean Biological Regulatory Networks.PLoS ONE 4(12):e7992.doi:10.1371/journal. pone.0007992 Editor:MarkIsalan,CenterforGenomicRegulation,Spain ReceivedSeptember18,2009;Accepted