Gunawan Rudiyanto, Cao Yang, Petzold Linda, Doyle Francis J
Department of Chemical Engineering, University of California, Santa Barbara, California, USA.
Biophys J. 2005 Apr;88(4):2530-40. doi: 10.1529/biophysj.104.053405. Epub 2005 Feb 4.
Sensitivity analysis quantifies the dependence of system behavior on the parameters that affect the process dynamics. Classical sensitivity analysis, however, does not directly apply to discrete stochastic dynamical systems, which have recently gained popularity because of its relevance in the simulation of biological processes. In this work, sensitivity analysis for discrete stochastic processes is developed based on density function (distribution) sensitivity, using an analog of the classical sensitivity and the Fisher Information Matrix. There exist many circumstances, such as in systems with multistability, in which the stochastic effects become nontrivial and classical sensitivity analysis on the deterministic representation of a system cannot adequately capture the true system behavior. The proposed analysis is applied to a bistable chemical system--the Schlögl model, and to a synthetic genetic toggle-switch model. Comparisons between the stochastic and deterministic analyses show the significance of explicit consideration of the probabilistic nature in the sensitivity analysis for this class of processes.
灵敏度分析量化了系统行为对影响过程动态的参数的依赖性。然而,经典灵敏度分析并不直接适用于离散随机动力系统,由于其在生物过程模拟中的相关性,这类系统近来颇受关注。在这项工作中,基于密度函数(分布)灵敏度,利用经典灵敏度的类似物和费希尔信息矩阵来开展离散随机过程的灵敏度分析。存在许多情形,比如在具有多重稳定性的系统中,随机效应变得显著,而对系统确定性表示的经典灵敏度分析无法充分捕捉真实的系统行为。所提出的分析方法应用于一个双稳化学系统——施洛格模型,以及一个合成基因开关模型。随机分析和确定性分析之间的比较表明,对于这类过程的灵敏度分析,明确考虑概率性质具有重要意义。