Reverse Engineering the Gap Gene Network of Drosophila melanogaster 英文参考文献.docVIP

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Reverse Engineering the Gap Gene Network of Drosophila melanogaster 英文参考文献.doc

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Reverse Engineering the Gap Gene Network of Drosophila melanogaster 英文参考文献

ReverseEngineeringtheGapGeneNetwork ofDrosophilamelanogaster Theodore J.Perkins1*,Johannes Jaeger2,3¤,John Reinitz2,3,Leon Glass4 1McGillCentreforBioinformatics,McGillUniversity,Montreal,Quebec,Canada,2DepartmentofAppliedMathematicsandStatistics,StonyBrookUniversity,StonyBrook, NewYork,UnitedStatesofAmerica,3CenterforDevelopmentalGenetics,StonyBrookUniversity,StonyBrook,NewYork,UnitedStatesofAmerica,4CentreforNonlinear Dynamics,DepartmentofPhysiology,McGillUniversity,Montreal,Quebec,Canada Afundamentalprobleminfunctionalgenomicsistodeterminethestructureanddynamicsofgeneticnetworksbased onexpressiondata.Wedescribeanewstrategyforsolvingthisproblemandapplyittorecentlypublisheddataon earlyDrosophilamelanogasterdevelopment.Ourmethodisordersofmagnitudefasterthancurrentfittingmethods andallowsustofitdifferenttypesofrulesforexpressingregulatoryrelationships.Specifically,weuseourapproachto fitmodelsusingasmoothnonlinearformalismformodelinggeneregulation(genecircuits)aswellasmodelsusing logicalrulesbasedonactivationandrepressionthresholdsfortranscriptionfactors.Ourtechniquealsoallowsusto infer regulatory relationships de novo or to test network structures suggested by the literature. We fit a series of modelstotestseveraloutstandingquestionsaboutgapgeneregulation,includingregulationofandbyhunchbackand the role of autoactivation. Based on our modeling results and validation against the experimental literature, we proposearevisednetworkstructureforthegapgenesystem.Interestingly,somerelationshipsinstandardtextbook models of gap gene regulation appear to be unnecessary for or even inconsistent with the details of gap gene expressionduringwild-typedevelopment. Citation:PerkinsTJ,JaegerJ,ReinitzJ,GlassL(2006)Reverseengineeringthegapgenenetworkof Drosophila melanogaster.PLoSComputBiol2(5):e51.DOI:10.1371/ journal.pcbi.0020051 example. Further, qualitative models typically provide little or no explanation of the timing or dynamics of expression, Introduction The segmente