Soliman Sylvain, Fages François, Radulescu Ovidiu
Inria, Domaine de Voluceau, Rocquencourt, 78150 France.
University of Montpellier 2, Place Eugene Bataillon, Montpellier, 34095 France.
Algorithms Mol Biol. 2014 Dec 4;9(1):24. doi: 10.1186/s13015-014-0024-2. eCollection 2014.
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.
模型约简是系统生物学和动力系统理论中的核心主题,例如用于降低详细模型的复杂性、寻找重要参数以及开发多尺度模型。虽然奇异摄动理论是分析动力系统不同时间尺度并据此分解系统的标准数学工具,但热带方法提供了一个简单的代数框架,以便在多项式系统中系统地执行这些分析。这些方法的关键在于热带平衡的计算。在本文中,我们表明基于约束的方法,使用具体化约束来表达平衡条件,使得数值求解标准计算方法无法解决的非线性热带平衡问题成为可能。我们首先通过对一个简单生化机制——米氏酶促反应模型进行详细约简来说明这种方法,其次通过在http://biomodels.net库上获得的大规模性能数据来说明。