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Sensitivity analysis of the reaction occurrence and recurrence times in steady-state biochemical networks
Mathematical Biosciences ( IF 4.3 ) Pub Date : 2020-12-02 , DOI: 10.1016/j.mbs.2020.108518
Diego Frezzato 1
Affiliation  

Continuous-time stationary Markov jump processes among discrete sites are encountered in disparate biochemical ambits. Sites and connecting dynamical events form a ‘network’ in which the sites are the available system’s states, and the events are site-to-site transitions, or even neutral processes in which the system does not change site but the event is however detectable. Examples include conformational transitions in single biomolecules, stochastic chemical kinetics in the space of the molecules copy numbers, and even macroscopic steady-state reactive mixtures if one adopts the viewpoint of a tagged molecule (or even of a molecular moiety) whose state may change when it is involved in a chemical reaction. Among the variety of dynamical descriptors, here we focus on the first occurrence times (starting from a given site) and on the recurrence times of an event of interest. We develop the sensitivity analysis for the lowest moments of the statistical distribution of such times with respect to the rate constants of the network. In particular, simple expressions and inequalities allow us to establish a direct relationship between selective variation of rate constants and effect on average times and variances. As illustrative cases we treat the substrate inhibition in enzymatic catalysis in which a tagged enzyme molecule jumps between three states, and the basic two-site model of stochastic gene expression in which the single gene switches between active and inactive forms.



中文翻译:

稳态生化网络中反应发生和重复时间的敏感性分析

在不同的生化范围中会遇到离散位点之间的连续时间平稳马尔可夫跳跃过程。站点和连接动态事件形成一个“网络”,其中站点是可用系统的状态,事件是站点到站点的转换,甚至是系统不更改站点但事件可检测的中立过程。例子包括单个生物分子中的构象转变,分子拷贝数空间中的随机化学动力学,甚至宏观稳态反应混合物,如果采用标记分子(或什至分子部分)的观点,其状态可能会在它参与化学反应。在各种动态描述符中,在这里,我们关注首次发生时间(从给定地点开始)和感兴趣事件的重复发生时间。我们针对这些时间的统计分布的最低时刻相对于网络的速率常数进行了敏感性分析。特别是,简单的表达式和不等式使我们能够在速率常数的选择性变化与对平均时间和方差的影响之间建立直接关系。作为说明性案例,我们处理酶催化中的底物抑制,其中标记的酶分子在三种状态之间跳跃,以及随机基因表达的基本双位点模型,其中单个基因在活性和非活性形式之间切换。我们针对这些时间的统计分布的最低时刻相对于网络的速率常数进行了敏感性分析。特别是,简单的表达式和不等式使我们能够在速率常数的选择性变化与对平均时间和方差的影响之间建立直接关系。作为说明性案例,我们处理酶催化中的底物抑制,其中标记的酶分子在三种状态之间跳跃,以及随机基因表达的基本双位点模型,其中单个基因在活性和非活性形式之间切换。我们针对这些时间的统计分布的最低时刻相对于网络的速率常数进行了敏感性分析。特别是,简单的表达式和不等式使我们能够在速率常数的选择性变化与对平均时间和方差的影响之间建立直接关系。作为说明性案例,我们处理酶催化中的底物抑制,其中标记的酶分子在三种状态之间跳跃,以及随机基因表达的基本双位点模型,其中单个基因在活性和非活性形式之间切换。

更新日期:2021-01-28
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