Dynamic Modelling under Uncertainty The Case of Trypanosoma brucei Energy Metabolism 英文参考文献.docVIP

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Dynamic Modelling under Uncertainty The Case of Trypanosoma brucei Energy Metabolism 英文参考文献.doc

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Dynamic Modelling under Uncertainty The Case of Trypanosoma brucei Energy Metabolism 英文参考文献

DynamicModellingunderUncertainty:TheCaseof TrypanosomabruceiEnergyMetabolism FionaAchcar1,2,EduardJ.Kerkhoven3,TheSilicoTrypConsortium,BarbaraM.Bakker4,MichaelP. Barrett3,RainerBreitling1,2* 1Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom, 2Groningen BioinformaticsCentre,GroningenBiomolecularSciencesandBiotechnologyInstitute,UniversityofGroningen,Groningen,TheNetherlands,3WellcomeTrustCentrefor Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom,4DepartmentofLiver,DigestiveandMetabolicDiseases,UniversityMedicalCentreGroningen,UniversityofGroningen,TheNetherlands Abstract Kineticmodelsofmetabolismrequiredetailedknowledgeofkineticparameters.However,duetomeasurementerrorsor lackofdatathisknowledgeisoftenuncertain.ThemodelofglycolysisintheparasiticprotozoanTrypanosomabruceiisa particularly well analysed example of a quantitative metabolic model, but so far it has been studied with a fixed set of parametersonly.Hereweevaluatetheeffectofparameteruncertainty.Inordertodefineprobabilitydistributionsforeach parameter, information about the experimental sources and confidence intervals for all parameters were collected. We created a wiki-based website dedicated to the detailed documentation of this information: the SilicoTryp wiki (http:// silicotryp.ibls.gla.ac.uk/wiki/Glycolysis).Usinginformationcollectedinthewiki,wethenassignedprobabilitydistributionsto allparametersofthemodel.Thisallowedustosamplesetsofalternativemodels,accuratelyrepresentingourdegreeof uncertainty.Somepropertiesofthemodel,suchastherepartitionoftheglycolyticfluxbetweentheglycerolandpyruvate producingbranches,arerobusttotheseuncertainties.However,ouranalysisalsoallowedustoidentifyfragilitiesofthe modelleadingtotheaccumulationof3-phosphoglycerateand/orpyruvate.Theanalysisofthecontrolcoefficie