论文标题

减少具有近似保护定律的化学反应网络

Reduction of Chemical Reaction Networks with Approximate Conservation Laws

论文作者

Desoeuvres, Aurélien, Iosif, Alexandru, Lüders, Christoph, Radulescu, Ovidiu, Rahkooy, Hamid, Seiß, Matthias, Sturm, Thomas

论文摘要

基于准稳态近似值的快速慢化学反应网络的模型减少在快速子系统具有第一个积分时失败。我们称这些第一个积分近似保护法。为了定义快速子系统并确定近似保护定律,我们使用热带几何形状的想法。我们证明,任何近似保护法的演变都比其中所有涉及的物种慢,因此代表了扩展系统中的补充缓慢变量。通过消除扩展系统的某些变量,我们获得没有近似保护定律的网络,可以通过标准的单数扰动方法来降低。近似保护法的应用领域涵盖了准平衡近似,在生物化学中众所周知。我们讨论减少慢速和多个时间尺度系统的减少。具有多个时间尺度的网络具有分层放松。在给定的时间尺度上,我们的多个时间尺度减少方法定义了三个子系统,由(i)奴隶的快速变量组成,满足代数方程,(ii)满足减少普通微分方程的缓慢驱动变量,(iii)淬灭了许多较慢的变量,这些变量是恒定的。快速变量满足的代数方程定义了嵌套正常的氢化歧管的链。在这样的链条中,更快的歧管具有更高的尺寸,并包含较慢的歧管。我们的还原方法是针对具有单一反应速率和线性,单一或多项式近似保护定律的网络引入的算法。我们提出了符号算法以重塑和重新塑造网络,以便可以将几何奇异扰动理论应用于它们,测试理论的适用性,并最终减少网络。作为概念证明,我们将此方法应用于TGF-B信号通路的模型。

Model reduction of fast-slow chemical reaction networks based on the quasi-steady state approximation fails when the fast subsystem has first integrals. We call these first integrals approximate conservation laws. In order to define fast subsystems and identify approximate conservation laws, we use ideas from tropical geometry. We prove that any approximate conservation law evolves slower than all the species involved in it and therefore represents a supplementary slow variable in an extended system. By elimination of some variables of the extended system, we obtain networks without approximate conservation laws, which can be reduced by standard singular perturbation methods. The field of applications of approximate conservation laws covers the quasi-equilibrium approximation, well known in biochemistry. We discuss reductions of slow-fast as well as multiple timescale systems. Networks with multiple timescales have hierarchical relaxation. At a given timescale, our multiple timescale reduction method defines three subsystems composed of (i) slaved fast variables satisfying algebraic equations, (ii) slow driving variables satisfying reduced ordinary differential equations, and (iii) quenched much slower variables that are constant. The algebraic equations satisfied by fast variables define chains of nested normally hyberbolic invariant manifolds. In such chains, faster manifolds are of higher dimension and contain the slower manifolds. Our reduction methods are introduced algorithmically for networks with monomial reaction rates and linear, monomial or polynomial approximate conservation laws. We propose symbolic algorithms to reshape and rescale the networks such that geometric singular perturbation theory can be applied to them, test the applicability of the theory, and finally reduce the networks. As a proof of concept, we apply this method to a model of the TGF-b signaling pathway.

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