School of Mathematics and Statistics, Newcastle University, Merz Court, Newcastle upon Tyne NE1 7RU, UK.
Interface Focus. 2011 Dec 6;1(6):807-20. doi: 10.1098/rsfs.2011.0047. Epub 2011 Sep 29.
Computational systems biology is concerned with the development of detailed mechanistic models of biological processes. Such models are often stochastic and analytically intractable, containing uncertain parameters that must be estimated from time course data. In this article, we consider the task of inferring the parameters of a stochastic kinetic model defined as a Markov (jump) process. Inference for the parameters of complex nonlinear multivariate stochastic process models is a challenging problem, but we find here that algorithms based on particle Markov chain Monte Carlo turn out to be a very effective computationally intensive approach to the problem. Approximations to the inferential model based on stochastic differential equations (SDEs) are considered, as well as improvements to the inference scheme that exploit the SDE structure. We apply the methodology to a Lotka-Volterra system and a prokaryotic auto-regulatory network.
计算系统生物学关注的是开发生物过程的详细机械模型。这些模型通常是随机的,难以进行分析,包含必须从时间序列数据中估计的不确定参数。在本文中,我们考虑推断随机动力学模型参数的任务,该模型定义为马尔可夫(跳跃)过程。对于复杂非线性多变量随机过程模型参数的推断是一个具有挑战性的问题,但我们在这里发现,基于粒子马尔可夫链蒙特卡罗的算法是解决该问题的非常有效的计算密集型方法。我们还考虑了基于随机微分方程 (SDE) 的推理模型的近似值,以及利用 SDE 结构改进推理方案。我们将该方法应用于 Lotka-Volterra 系统和原核自动调节网络。