Shrinking the Metabolic Solution Space Using Experimental Datasets 英文参考文献.docVIP

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Shrinking the Metabolic Solution Space Using Experimental Datasets 英文参考文献.doc

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Shrinking the Metabolic Solution Space Using Experimental Datasets 英文参考文献

Review ShrinkingtheMetabolicSolutionSpaceUsing ExperimentalDatasets JenniferL.Reed* DepartmentofChemicalandBiologicalEngineering,UniversityofWisconsin–Madison,Madison,Wisconsin,UnitedStatesofAmerica model’s solution space,whichcan be queriedusing anumber of Abstract: Constraint-based models of metabolism have been used in a variety of studies on drug discovery, metabolic engineering, evolution, and multi-species interactions. These genome-scale models can be gener- ated for any sequenced organism since their main parameters (i.e., reaction stoichiometry) are highly con- served.Theirrelativelylowparameterrequirementmakes these models easy to develop; however, these models oftenresultinasolutionspacewithmultiplepossibleflux distributions,makingitdifficulttodeterminetheprecise flux state in the cell. Recent research efforts in this modeling field have investigated how additional experi- mental data, including gene expression, protein expres- sion, metabolite concentrations, and kinetic parameters, can be used to reduce the solution space. This mini- review providesasummary ofthedata-driven computa- tional approaches that are available for reducing the solution space and thereby improve predictions of intracellularfluxesbyconstraint-basedmodels. approaches [15]. Most of these constraints-based approaches utilizeoptimizationtoidentifyasubsetofsolutionsofinterestfrom within thesolution space that are predicted tobe physiologically relevant.Forexample,fluxbalanceanalysis(FBA)isoftenusedto identifyfluxdistributionsthatmaximizebiomassyields[16]. Giventhenon-uniquenessofconstraint-basedmodelsolutions, a growing number of methods have focused recently on incorporating additional constraints to reduce the solution space and thereby improve the precision and accuracy of model predictions. This editorial reviews recent methods that utilize additionalbiologicalinformation(e.g.,geneorproteinexpression, metabolite concentrations, and kinetic parameters) to further restric