Global sensitivity analysis in dynamic metabolic networks

In this work, we have performed global sensitivity analysis on a large-scale dynamic metabolic network through variance-based techniques. Time profiles for sensitivity indices have been calculated for each parameter, based on Sobol' approach (2001). The global sensitivity analysis has been carried out on a dynamic model for the Embden-Meyerhof-Parnas pathway, the phosphotransferase system and the pentose-phosphate pathway of Escherichia coli K-12 strain W3110 (Chassagnole et al., 2002). The model comprises eighteen dynamic mass balance equations for extracellular glucose and intracellular metabolites, thirty kinetic rate expressions and seven additional algebraic equations that represent concentration profiles for co-metabolites. Each parameter has been considered to have a normal probability distribution centered on its nominal value and sample sizes of two thousand and five hundred scenarios have been considered. The preceding analysis has allowed identification of eleven parameters as the most influential ones on the complex metabolic network under study. (C) 2010 Elsevier Ltd. All rights reserved.