We present two modifications of the flux balance analysis (FBA) metabolic modeling framework which relax implicit assumptions of the biomass reaction. Our flexible flux balance analysis (flexFBA) objective removes the fixed proportion between reactants, and can therefore produce a subset of biomass reactants. Our time-linked flux balance analysis (tFBA) simulation removes the fixed proportion between reactants and byproducts, and can therefore describe transitions between metabolic steady states. Used together, flexFBA and tFBA model a time scale shorter than the regulatory and growth steady state encoded by the biomass reaction. This combined short-time FBA method is intended for integrated modeling applications to enable detailed and dynamic depictions of microbial physiology such as whole- cell modeling. For example, when modeling Escherichia coli, it avoids artifacts caused by low-copy- number enzymes in single-cell models with kinetic bounds. Even outside integrated modeling contexts, the detailed predictions of flexFBA and tFBA complement existing FBA techniques. We show detailed metabolite production of in silico knockouts used to identify when correct essentiality predictions are made for the wrong reason.
Reproduce publication results for methods flexible and time-linked Flux Balance Analysis (flexFBA and tFBA). Additionally a minimal flexFBA example using Matlab Cobra Toolbox formatted models.
(provided for computational biologists to reproduce publication results, and a small utility written for example use with the Cobra toolbox) The associated publication describes two complimentary methods that remove the inherent long-time assumptions of the biomass reaction used in FBA. Implementing a flexible objective flexFBA, enables a metabolic network to produce biological process reactants independently from one another. This flexibility is in contrast to the rigid proportion held by the traditional biomass reaction of FBA. Also, time-linked simulation (tFBA) can represent transitions between metabolic steady states by returning cell process byproducts at subsequent time-steps.
Reproduction of publication simulations and figures, including virtual machine in which to run (not intended as software). MatLab script for using flexFBA for troubleshooting COBRA format models.See all Downloads