Incorporating age and delay into models for biophysical systems.

Incorporating age and delay into models for biophysical systems.
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DOI:
10.1088/1478-3975/abc2ab
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发表时间:
2021-02-13
期刊:
影响因子:
2
通讯作者:
--
中科院分区:
生物学4区
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在许多生物系统中,化学反应或物理状态的变化被认为是瞬间发生的。为了描述这些系统的动态,马尔可夫模型,需要指数分布的事件间的时间已被广泛使用。然而,一些生物物理过程,如基因转录和翻译,已知有一个显着的差距之间的启动和完成的过程,这使得指数分布的通常假设是站不住脚的。在本文中,我们考虑放宽这一假设,将年龄相关的随机时间延迟(根据给定的概率分布分布)到系统动力学。我们通过在一个更抽象的状态空间上构造一个测度值马尔可夫过程来实现这一点,这使我们能够跟踪参与化学反应的分子的“年龄”。我们研究了这种年龄结构系统的大容量极限。我们表明,当适当的缩放,随机系统可以近似为一个系统的偏微分方程(PDE)在大容量的限制,而不是常微分方程(ODE)在经典理论。我们展示了如何限制PDE系统可以用于进一步的模型简化的目的,并设计有效的仿真算法。为了描述这些想法,我们使用一个简单的转录过程作为运行示例。然而,我们注意到,本文中开发的方法适用于广泛的一类生物物理系统。
In many biological systems, chemical reactions or changes in a physical state are assumed to occur instantaneously. For describing the dynamics of those systems, Markov models that require exponentially distributed inter-event times have been used widely. However, some biophysical processes such as gene transcription and translation are known to have a significant gap between the initiation and the completion of the processes, which renders the usual assumption of exponential distribution untenable. In this paper, we consider relaxing this assumption by incorporating age-dependent random time delays (distributed according to a given probability distribution) into the system dynamics. We do so by constructing a measure-valued Markov process on a more abstract state space, which allows us to keep track of the “ages” of molecules participating in a chemical reaction. We study the large-volume limit of such age-structured systems. We show that, when appropriately scaled, the stochastic system can be approximated by a system of Partial Differential Equations (PDEs) in the large-volume limit, as opposed to Ordinary Differential Equations (ODEs) in the classical theory. We show how the limiting PDE system can be used for the purpose of further model reductions and for devising efficient simulation algorithms. In order to describe the ideas, we use a simple transcription process as a running example. We, however, note that the methods developed in this paper apply to a wide class of biophysical systems.
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