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BMC Systems Biology

, 5:129

First Online: 16 August 2011Received: 10 August 2010Accepted: 16 August 2011

Abstract

BackgroundThe ability to perform quantitative studies using isotope tracers and metabolic flux analysis MFA is critical for detecting pathway bottlenecks and elucidating network regulation in biological systems, especially those that have been engineered to alter their native metabolic capacities. Mathematically, MFA models are traditionally formulated using separate state variables for reaction fluxes and isotopomer abundances. Analysis of isotope labeling experiments using this set of variables results in a non-convex optimization problem that suffers from both implementation complexity and convergence problems.

ResultsThis article addresses the mathematical and computational formulation of C MFA models using a new set of variables referred to as fluxomers. These composite variables combine both fluxes and isotopomer abundances, which results in a simply-posed formulation and an improved error model that is insensitive to isotopomer measurement normalization. A powerful fluxomer iterative algorithm FIA is developed and applied to solve the MFA optimization problem. For moderate-sized networks, the algorithm is shown to outperform the commonly used 13CFLUX cumomer-based algorithm and the more recently introduced OpenFLUX software that relies upon an elementary metabolite unit EMU network decomposition, both in terms of convergence time and output variability.

ConclusionsSubstantial improvements in convergence time and statistical quality of results can be achieved by applying fluxomer variables and the FIA algorithm to compute best-fit solutions to MFA models. We expect that the fluxomer formulation will provide a more suitable basis for future algorithms that analyze very large scale networks and design optimal isotope labeling experiments.

Electronic supplementary materialThe online version of this article doi:10.1186-1752-0509-5-129 contains supplementary material, which is available to authorized users.

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Autor: Orr Srour - Jamey D Young - Yonina C Eldar

Fuente: https://link.springer.com/







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