Flux coupling analysis of genome-scale metabolic network reconstructions

Anthony P. Burgard, Evgeni V. Nikolaev, Christophe H. Schilling, Costas D. Maranas

Research output: Contribution to journalArticle

276 Scopus citations

Abstract

In this paper, we introduce the Flux Coupling Finder (FCF) framework for elucidating the topological and flux connectivity features of genome-scale metabolic networks. The framework is demonstrated on genome-scale metabolic reconstructions of Helicobacter pylori, Escherichia coli, and Saccharomyces cerevisiae. The analysis allows one to determine whether any two metabolic fluxes, v1 and v2, are (1) directionally coupled, if a non-zero flux for v1 implies a non-zero flux for v2 but not necessarily the reverse; (2) partially coupled, if a non-zero flux for v1 implies a non-zero, though variable, flux for v2 and vice versa; or (3) fully coupled, if a non-zero flux for v1 implies not only a non-zero but also a fixed flux for v2 and vice versa. Flux coupling analysis also enables the global identification of blocked reactions, which are all reactions incapable of carrying flux under a certain condition; equivalent knockouts, defined as the set of all possible reactions whose deletion forces the flux through a particular reaction to zero; and sets of affected reactions denoting all reactions whose fluxes are forced to zero if a particular reaction is deleted. The FCF approach thus provides a novel and versatile tool for aiding metabolic reconstructions and guiding genetic manipulations.

Original languageEnglish (US)
Pages (from-to)301-312
Number of pages12
JournalGenome research
Volume14
Issue number2
DOIs
StatePublished - Feb 1 2004

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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