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Time-dependent propagators for stochastic models of gene expression: an analytical method

机译:基于时间的传播子用于基因表达的随机模型:一种分析方法

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摘要

The inherent stochasticity of gene expression in the context of regulatory networks profoundly influences the dynamics of the involved species. Mathematically speaking, the propagators which describe the evolution of such networks in time are typically defined as solutions of the corresponding chemical master equation (CME). However, it is not possible in general to obtain exact solutions to the CME in closed form, which is due largely to its high dimensionality. In the present article, we propose an analytical method for the efficient approximation of these propagators. We illustrate our method on the basis of two categories of stochastic models for gene expression that have been discussed in the literature. The requisite procedure consists of three steps: a probability-generating function is introduced which transforms the CME into (a system of) partial differential equations (PDEs); application of the method of characteristics then yields (a system of) ordinary differential equations (ODEs) which can be solved using dynamical systems techniques, giving closed-form expressions for the generating function; finally, propagator probabilities can be reconstructed numerically from these expressions via the Cauchy integral formula. The resulting ‘library’ of propagators lends itself naturally to implementation in a Bayesian parameter inference scheme, and can be generalised systematically to related categories of stochastic models beyond the ones considered here.
机译:在调控网络的背景下,基因表达的内在随机性深刻地影响了所涉及物种的动态。从数学上讲,描述此类网络随时间演变的传播子通常被定义为相应化学主方程(CME)的解。但是,通常不可能获得封闭形式的CME的精确解,这在很大程度上是由于其尺寸大。在本文中,我们提出了一种有效逼近这些传播子的分析方法。我们根据文献中讨论过的两类基因表达的随机模型来说明我们的方法。必要的过程包括三个步骤:引入概率生成函数,该函数将CME转换为偏微分方程(PDE)(的系统);然后,通过使用特征方法,可以得出(一个系统)常微分方程组(ODE),可以使用动力学系统技术对其进行求解,从而给出生成函数的闭式表达式;最后,可以通过柯西积分公式从这些表达式中数值地重建传播概率。由此产生的传播者“库”很自然地适合于贝叶斯参数推断方案的实现,并且可以系统地推广到随机模型的相关类别,而不是此处考虑的类别。

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