Estimating the Stochastic Bifurcation Structure of Cellular Networks 英文参考文献.docVIP

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Estimating the Stochastic Bifurcation Structure of Cellular Networks 英文参考文献.doc

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Estimating the Stochastic Bifurcation Structure of Cellular Networks 英文参考文献

EstimatingtheStochasticBifurcationStructureof CellularNetworks CarlSong1,HilaryPhenix2,3,VidaAbedi2,3,MatthewScott4,BrianP.Ingalls4,MadsK?rn2,3,5*, TheodoreJ.Perkins1,6 * 1OttawaHospitalResearchInstitute,Ottawa,Ontario,Canada,2DepartmentofCellularandMolecularMedicine,UniversityofOttawa,Ottawa,Ontario,Canada,3Ottawa InstituteofSystemsBiology,UniversityofOttawa,Ottawa,Ontario,Canada,4DepartmentofAppliedMathematics,UniversityofWaterloo,Waterloo,Ontario,Canada, 5Department ofPhysics,UniversityofOttawa,Ottawa,Ontario,Canada, 6Department ofBiochemistry,MicrobiologyandImmunology, UniversityofOttawa,Ottawa, Ontario,Canada Abstract High throughput measurement of gene expression at single-cell resolution, combined with systematic perturbation of environmentalorcellularvariables,providesinformationthatcanbeusedtogeneratenovelinsightintothepropertiesof generegulatorynetworksbylinkingcellularresponsestoexternalparameters.Indynamicalsystemstheory,thisinformation is the subject of bifurcation analysis, which establishes how system-level behaviour changes as a function of parameter values within a given deterministic mathematical model. Since cellular networks are inherently noisy, we generalize the traditional bifurcation diagram of deterministic systems theory to stochastic dynamical systems. We demonstrate how statisticalmethodsfordensityestimation,inparticular,mixturedensityandconditionalmixturedensityestimators,canbe employedtoestablishempiricalbifurcationdiagramsdescribingthebistablegeneticswitchnetworkcontrollinggalactose utilization in yeast Saccharomyces cerevisiae. These approaches allow us to make novel qualitative and quantitative observations about the switching behavior of the galactose network, and provide a framework that might be useful to extractinformationneededforthedevelopmentofquantitativenetworkmodels. Citation:SongC,PhenixH,AbediV,ScottM,IngallsBP,etal.(2010)EstimatingtheStochasticBifurcationStructureofCellularNetworks.PLoSComputBiol6(3): e1000699.doi