NDLI: Prediction of metabolic fluxes by incorporating genomic context and flux-converging pattern analyses

Content Provider	PubMed Central
Author	Park, Jong Myoung Kim, Tae Yong Lee, Sang Yup
Abstract	Flux balance analysis (FBA) of a genome-scale metabolic model allows calculation of intracellular fluxes by optimizing an objective function, such as maximization of cell growth, under given constraints, and has found numerous applications in the field of systems biology and biotechnology. Due to the underdetermined nature of the system, however, it has limitations such as inaccurate prediction of fluxes and existence of multiple solutions for an optimal objective value. Here, we report a strategy for accurate prediction of metabolic fluxes by FBA combined with systematic and condition-independent constraints that restrict the achievable flux ranges of grouped reactions by genomic context and flux-converging pattern analyses. Analyses of three types of genomic contexts, conserved genomic neighborhood, gene fusion events, and co-occurrence of genes across multiple organisms, were performed to suggest a group of fluxes that are likely on or off simultaneously. The flux ranges of these grouped reactions were constrained by flux-converging pattern analysis. FBA of the Escherichia coli genome-scale metabolic model was carried out under several different genotypic (pykF, zwf, ppc, and sucA mutants) and environmental (altered carbon source) conditions by applying these constraints, which resulted in flux values that were in good agreement with the experimentally measured 13C-based fluxes. Thus, this strategy will be useful for accurately predicting the intracellular fluxes of large metabolic networks when their experimental determination is difficult.
Related Links	http://dx.doi.org/10.1073/pnas.1003740107
Ending Page	14936
Page Count	6
Starting Page	14931
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	33
Volume Number	107
Language	English
Publisher	National Academy of Sciences
Publisher Date	2010-08-17
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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