Email updates

Keep up to date with the latest news and content from BMC Systems Biology and BioMed Central.

Open Access Methodology article

Fluxomers: a new approach for 13C metabolic flux analysis

Orr Srour1, Jamey D Young2* and Yonina C Eldar1*

Author Affiliations

1 Dept. of Electrical Engineering, Technion-Israel Institute of Technology, 32000 Haifa, Israel

2 Department of Chemical and Biomolecular Engineering, Vanderbilt University, TN, USA

For all author emails, please log on.

BMC Systems Biology 2011, 5:129  doi:10.1186/1752-0509-5-129

Published: 16 August 2011

Abstract

Background

The 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.

Results

This article addresses the mathematical and computational formulation of 13C 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.

Conclusions

Substantial 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.