An exact arithmetic toolbox for a consistent and reproducible structural analysis of metabolic network models.

Nat Commun
Authors
Keywords
Abstract

Constraint-based models are currently the only methodology that allows the study of metabolism at the whole-genome scale. Flux balance analysis is commonly used to analyse constraint-based models. Curiously, the results of this analysis vary with the software being run, a situation that we show can be remedied by using exact rather than floating-point arithmetic. Here we introduce MONGOOSE, a toolbox for analysing the structure of constraint-based metabolic models in exact arithmetic. We apply MONGOOSE to the analysis of 98 existing metabolic network models and find that the biomass reaction is surprisingly blocked (unable to sustain non-zero flux) in nearly half of them. We propose a principled approach for unblocking these reactions and extend it to the problems of identifying essential and synthetic lethal reactions and minimal media. Our structural insights enable a systematic study of constraint-based metabolic models, yielding a deeper understanding of their possibilities and limitations.

Year of Publication
2014
Journal
Nat Commun
Volume
5
Pages
4893
Date Published
2014 Oct 07
ISSN
2041-1723
URL
DOI
10.1038/ncomms5893
PubMed ID
25291352
PubMed Central ID
PMC4205847
Links
Grant list
R01 GM108348 / GM / NIGMS NIH HHS / United States
GM108348 / GM / NIGMS NIH HHS / United States
Howard Hughes Medical Institute / United States