Flux coupling analysis of genome-scale metabolic network reconstructions.
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.
Burgard
Anthony P
AP
Department of Chemical Engineering, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Nikolaev
Evgeni V
EV
Schilling
Christophe H
CH
Maranas
Costas D
CD
D000332:Aerobiosis / Q000235:genetics; D000693:Anaerobiosis / Q000235:genetics; D018533:Biomass; D019295:Computational Biology / Q000379:methods; D004269:DNA, Bacterial; D004271:DNA, Fungal; D004734:Energy Metabolism / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D016680:Genome, Bacterial; D016681:Genome, Fungal; D005947:Glucose / Q000378:metabolism; D016480:Helicobacter pylori / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D008954:Models, Biological; D011687:Purines / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
D004269:DNA, Bacterial; D004271:DNA, Fungal; D011687:Purines; D005947:Glucose; C030985:purine