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一种用于随机反应网络稳态灵敏度分析的有限状态投影方法。

A finite state projection method for steady-state sensitivity analysis of stochastic reaction networks.

机构信息

Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.

出版信息

J Chem Phys. 2019 Apr 7;150(13):134101. doi: 10.1063/1.5085271.

Abstract

Consider the standard stochastic reaction network model where the dynamics is given by a continuous-time Markov chain over a discrete lattice. For such models, estimation of parameter sensitivities is an important problem, but the existing computational approaches to solve this problem usually require time-consuming Monte Carlo simulations of the reaction dynamics. Therefore, these simulation-based approaches can only be expected to work over finite time-intervals, while it is often of interest in applications to examine the sensitivity values at the steady-state after the Markov chain has relaxed to its stationary distribution. The aim of this paper is to present a computational method for the estimation of steady-state parameter sensitivities, which instead of using simulations relies on the recently developed stationary finite state projection algorithm [Gupta et al., J. Chem. Phys. 147, 154101 (2017)] that provides an accurate estimate of the stationary distribution at a fixed set of parameters. We show that sensitivity values at these parameters can be estimated from the solution of a Poisson equation associated with the infinitesimal generator of the Markov chain. We develop an approach to numerically solve the Poisson equation, and this yields an efficient estimator for steady-state parameter sensitivities. We illustrate this method using several examples.

摘要

考虑标准的随机反应网络模型,其中动力学由离散格点上的连续时间马尔可夫链给出。对于这样的模型,参数敏感性的估计是一个重要的问题,但现有的解决这个问题的计算方法通常需要对反应动力学进行耗时的蒙特卡罗模拟。因此,这些基于模拟的方法通常只能在有限的时间间隔内工作,而在应用中,通常需要在马尔可夫链松弛到其平稳分布后,检查稳态下的敏感性值。本文的目的是提出一种用于估计稳态参数敏感性的计算方法,该方法不使用模拟,而是依赖于最近开发的稳态有限状态投影算法[Gupta 等人,J. Chem. Phys. 147, 154101 (2017)],该算法可以在固定参数集上提供平稳分布的精确估计。我们表明,可以从与马尔可夫链的无穷小生成器相关的泊松方程的解中估计这些参数的敏感性值。我们开发了一种数值求解泊松方程的方法,这为稳态参数敏感性提供了一种有效的估计器。我们使用几个例子来说明这种方法。

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