A constraint solving approach to model reduction by tropical equilibration

Abstract

Model reduction is a central topic in systems biology and dynamical systems theory, for reducing the complexity of detailed models, finding important parameters, and developing multi-scale models for instance. While singular perturbation theory is a standard mathematical tool to analyze the different time scales of a dynamical system and decompose the system accordingly, tropical methods provide a simple algebraic framework to perform these analyses systematically in polynomial systems. The crux of these methods is in the computation of tropical equilibrations. In this paper we show that constraint-based methods, using reified constraints for expressing the equilibration conditions, make it possible to numerically solve non-linear tropical equilibration problems, out of reach of standard computation methods. We illustrate this approach first with the detailed reduction of a simple biochemical mechanism, the Michaelis-Menten enzymatic reaction model, and second, with large-scale performance figures obtained on the http://biomodels.net repository.