RT Journal
A1 Burgard, Anthony P.
A1 Nikolaev, Evgeni V.
A1 Schilling, Christophe H.
A1 Maranas, Costas D.
T1 Flux Coupling Analysis of Genome-Scale Metabolic Network Reconstructions
JF Genome Research 
JO Genome Research 
YR 2004 
FD February 01 
VO 14 
IS 2 
SP 301 
OP 312 
DO 10.1101/gr.1926504 
UL http://genome.cshlp.org/content/14/2/301.abstract 
AB 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.