基因调控网络

纲要必要的说明问题与背景模型与仿真总结与展望参考文献有向图Bayesian网络Boolean网络及推广常微分方程“定性”微分方程偏微分方程随机模型基于规则的形式方法必要的说明我完全不懂生物学；我为什么要讲这个？我讲的侧重点在哪？内容完全基于：〔童维上传〕ModelingandSimulationofGeneticRegulatorySystems:ALiteratureReview问题与背景什么是基因调控网络？细胞、DNA、蛋白质、基因、基因网络为什么要研究基因调控网络？从分子水平认识细胞组织的功能。基因调控网络与复杂性了解基因调控网络，对我们有什么启发？问题与背景基因和蛋白质Genescodeforproteinsthatareessentialfordevelopmentandfunctioningoforganism:geneexpression问题与背景基因表达的调控：〔不同层次〕Geneexpressioncontrolledbyproteinsproducedbyothergenes:regulatoryinteractions问题与背景基因调控网络：Geneticregulatorynetworkconsistsofsetofgenes,proteins,smallmolecules,andtheirmutualregulatoryinteractions。Developmentandfunctioningoforganismscellemergesfrominteractionsingeneticregulatorynetworks。问题与背景例子：Choicebetweenalternativedevelopmentalpathwayscontrolledbynetworkofgenes,proteins,andmutualregulatoryinteractions。问题与背景基因调控网络的复杂性LargenetworksComplexcellshasmanycomponentsthatcaninteractincomplexways.Dynamicsprocessesarehardtounderstandbyintuitiveapproachesalone.Geneticregulatorynetworkshavecomplicatedinteractionsfarbeyondcorrelationofgeneexpressionpatterns.Clusteringcannotrevealcausalconnectionsbetweengenes.为什么需要数学建模与仿真？preciseandunambiguousdescriptionofnetworkofinteractionssystematicalderivationofbehavioralpredictions问题与背景目标－－我们想知道：Whichgenesareexpressed?

Whenandwhereintheorganisms?

Towhichextent?Arethereanyuniversallaws?Canwepredicttheevolutionofthenetwork?Howtopredicttheevolutionofthenetwork?问题与背景途径－－实验、建模、仿真：模型：有向图模型：有向图模型：Baysiannetwork模型：Baysiannetwork模型：Booleannetwork模型：Booleannetwork模型：Booleannetwork

Truthtables

State-transitiondiagram模型：Generalized

logicalnetwork模型：NonlinearODE模型：NonlinearODENegativefeedbackGeneencodesaproteininhibitingitsownexpressionimportantforhomeostasis,maintenanceofsystemnearadesiredstateSteadystateanalysisTransientbehaviorsimulation模型：NonlinearODEPositivefeedbackGeneencodesaproteinactivatingitsownexpression.importantfordifferentiation,evolutiontowardsoneoftwoalternativestatesofsystemSteadystatesTransientbehaviors模型：NonlinearODEApplications:模型：Piecewise-linearODE模型：QualitativeDifferentialEquationQDE:AbstractionoftheformQualitativevalue

x:Qualitativefunctionfi:QSIMalgorithmQualitativebehaviorsQualitativesimulation模型：SpatiallyDistributedModelConfiguration：Discretemodel:Continuousmodel:

boundaryconditions:模型：StochasticModel模型：StochasticModelTimeevolutionofp(X,t)：

masterequation:

＝>Stochasticsimulation:user.v.τandρ模型：StochasticModelSimulations:Applications:模型：Rule-basedformalismKnowledgebase〔Expertsystem?〕Facts：Rules：总结与展望总结与展望ComputertoolsformodelingandsimulationwillbenecessarytounderstandgeneticregulatoryprocessesVarietyofapproachesavailable,representinggeneticregulatorysystemsondifferentlevelsofabstractionChoiceofapproachdependsonaimofanalysisandonavailableinformation:knowledgeonreactionmechanismsquantitativedataonmodelparametersandgeneexpressionlevelsSeriousapplicationsarebeginningtoemerge参考文献HiddeDeJong,ModelingandSimulationofGeneticRegulatorySystems:ALiteratureReview,JournalOfComputationalBiology,9(1),2002.HarleyH.McAdams,AdamArkin,SimulationOfProkaryoticGeneticCircuits,Annu.Rev.Biophys.Biomol.Struct.1998.27:199–224.PaulSmolen,DouglasA.BaxterAndJohnH.Byrne,Modeling

TranscriptionalControlinGeneNetworks—Methods,RecentResults,andFutureDirections,BulletinofMathematicalBiology(2000)62,247–292.ChristopheRoos,FacingBiologicalComplexity–FromOneCelltoaMulticellularOrganism,TechnologyBIOINFORMATICS.EricAlmandAdamPArkin,Biologicalnetworks,CurrentOpinioninStructu