Pontificia Universidad Católica de Chile Pontificia Universidad Católica de Chile
Matos M., Saa P., Cowie N., Volkova S., De Leeuw M., Nielsen L. (2022)

GRASP: A computational platform for building kinetic models of cell metabolism

Revista : Bioinformatics Advances
Tipo de publicación : ISI Ir a publicación


Kinetic models of metabolism are crucial to understand the inner workings of cell metabolism. By taking into account enzyme regulation, detailed kinetic models can provide accurate predictions of metabolic fluxes. Comprehensive consideration of kinetic regulation requires highly parameterized non-linear models, which are challenging to build and fit using available modelling tools. Here, we present a computational package implementing the GRASP framework for building detailed kinetic models of cellular metabolism. By defining the mechanisms of enzyme regulation and a reference state described by reaction fluxes and their corresponding Gibbs free energy ranges, GRASP can efficiently sample an arbitrarily large population of thermodynamically feasible kinetic models. If additional experimental data are available (fluxes, enzyme and metabolite concentrations), these can be integrated to generate models that closely reproduce these observations using an Approximate Bayesian Computation fitting framework. Within the same framework, model selection tasks can be readily performed.