Using a Hybrid Genetic Algorithm and Fuzzy Logic for Metabolic Modeling

John Yen, Bogju Lee, James C. Liao

The identification of metabolic systems is a complex task due to the complexity of the system and limited knowledge about the model. Mathematical equations and ODE’s have been used to capture the structure of the model, and the conventional optimization techniques have been used to identify the parameters of the model. In general, however, a pure mathematical formulation of the model is difficult due to parametric uncertainty and incomplete knowledge of mechanisms. In this paper, we propose a modeling approach that (1) uses fuzzy rule-based model to augment algebraic enzyme models that are incomplete, and (2) uses a hybrid genetic algorithm to identify uncertain parameters in the model. The hybrid genetic algorithm (GA) integrates a GA with the simplex method in functional optimization to improve the GA’s convergence rate. We have applied this approach to modeling the rate of three enzyme reactions in E. coli central metabolism. The proposed modeling strategy allows (1) easy incorporation of qualitative insights into a pure mathematical model and (2) adaptive identification and optimization of key parameters to fit system behaviors observed in biochemical experiments.

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