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Genome Res. 2004 Feb;14(2):301-12. Epub 2004 Jan 12.

Flux coupling analysis of genome-scale metabolic network reconstructions.

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  • 1Department of Chemical Engineering, Pennsylvania State University, University Park, Pennsylvania 16802, USA.


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, v(1) and v(2), are (1) directionally coupled, if a non-zero flux for v(1) implies a non-zero flux for v(2) but not necessarily the reverse; (2) partially coupled, if a non-zero flux for v(1) implies a non-zero, though variable, flux for v(2) and vice versa; or (3) fully coupled, if a non-zero flux for v(1) implies not only a non-zero but also a fixed flux for v(2) 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.

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