Aug 4, 2010

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

Proceedings of the National Academy of Sciences of the United States of America
Jong Myoung ParkSang Yup Lee

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 s...Continue Reading

  • References43
  • Citations29

Mentioned in this Paper

Metabolic Process, Cellular
Alkalescens-Dispar Group
Genome
Metabolic Networks
Metabolic Networks and Pathways
Protoplasm
Vitreous Carbon
Gene Fusion Abnormality
Genomics
Cell Growth

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