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A moment-convergence method for stochastic analysis of biochemical reaction networks

机译:用于生化反应网络随机分析的矩收敛方法

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摘要

Traditional moment-closure methods need to assume that high-order cumulants of a probability distribution approximate to zero. However, this strong assumption is not satisfied for many biochemical reaction networks. Here, we introduce convergent moments (defined in mathematics as the coefficients in the Taylor expansion of the probability-generating function at some point) to overcome this drawback of the moment-closure methods. As such, we develop a new analysis method for stochastic chemical kinetics. This method provides an accurate approximation for the master probability equation (MPE). In particular, the connection between low-order convergent moments and rate constants can be more easily derived in terms of explicit and analytical forms, allowing insights that would be difficult to obtain through direct simulation or manipulation of the MPE. In addition, it provides an accurate and efficient way to compute steady-state or transient probability distribution, avoiding the algorithmic difficulty associated with stiffness of the MPE due to large differences in sizes of rate constants. Applications of the method to several systems reveal nontrivial stochastic mechanisms of gene expression dynamics, e.g., intrinsic fluctuations can induce transient bimodality and amplify transient signals, and slow switching between promoter states can increase fluctuations in spatially heterogeneous signals. The overall approach has broad applications in modeling, analysis, and computation of complex biochemical networks with intrinsic noise.
机译:传统的矩量闭合方法需要假设概率分布的高阶累积量接近零。然而,对于许多生化反应网络来说,这种强有力的假设并不令人满意。在这里,我们引入收敛矩(在数学上定义为概率生成函数在某些点的泰勒展开式中的系数)以克服矩闭合方法的这一缺点。因此,我们开发了一种新的随机化学动力学分析方法。此方法为主概率方程(MPE)提供了精确的近似值。特别是,低阶收敛矩与速率常数之间的联系可以通过显式和解析形式更容易地得出,从而获得直接通过MPE的直接仿真或操纵难以获得的见解。此外,它提供了一种准确有效的方法来计算稳态或瞬态概率分布,避免了由于速率常数大小的巨大差异而导致与MPE的刚度相关的算法困难。该方法在几个系统上的应用揭示了基因表达动力学的非平凡随机机制,例如,内在波动可以诱导瞬时双峰性并放大瞬时信号,启动子状态之间的缓慢切换可以增加空间异质信号的波动。总体方法在具有固有噪声的复杂生化网络的建模,分析和计算中具有广泛的应用。

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