Flux Coupling Analysis of Genome-Scale Metabolic Network Reconstructions
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.
Footnotes
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[Supplemental material is available online at www.genome.org.]
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Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.1926504. Article published online before print in January 2004.
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↵3 These authors contributed equally to this work.
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↵4 Corresponding author. E-MAIL costas{at}psu.edu; FAX (814) 865-7846.
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- Accepted November 24, 2003.
- Received September 1, 2003.
- Cold Spring Harbor Laboratory Press