Metabolic Network Reconstruction and Modeling

Christopher Le, Leonid Chindelevitch

The modeling of metabolic networks has seen a rapid expansion following the complete sequencing of thousands of genomes. The constraint-based modeling framework has emerged as one of the most popular approaches to reconstructing and analyzing genome-scale metabolic models. Its main assumption is that of a quasi-steady-state, requiring that the production of each internal metabolite be balanced by its consumption. However, due to the multiscale nature of the models, the large number of reactions and metabolites, and the use of floating-point arithmetic for the stoichiometric coefficients, ensuring that this assumption holds can be challenging.The MONGOOSE toolbox addresses this problem by using rational arithmetic, thus ensuring that models are analyzed in a reproducible manner and consistently with modeling assumptions. In this chapter we present a protocol for the complete analysis of a metabolic network model using the MONGOOSE toolbox, via its newly developed GUI, and describe how it can be used as a model-checking platform both during and after the model construction process.