Cramer-Rao bound and absolute sensitivity in chemical reaction networks

Dimitri Loutchko, Yuki Sughiyama, Tetsuya J. Kobayashi
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Abstract

Chemical reaction networks (CRN) comprise an important class of models to understand biological functions such as cellular information processing, the robustness and control of metabolic pathways, circadian rhythms, and many more. However, any CRN describing a certain function does not act in isolation but is a part of a much larger network and as such is constantly subject to external changes. In [Shinar, Alon, and Feinberg. "Sensitivity and robustness in chemical reaction networks." SIAM J App Math (2009): 977-998.], the responses of CRN to changes in the linear conserved quantities, called sensitivities, were studied in and the question of how to construct absolute, i.e., basis-independent, sensitivities was raised. In this article, by applying information geometric methods, such a construction is provided. The idea is to track how concentration changes in a particular chemical propagate to changes of all the other chemicals within a steady state. This is encoded in the matrix of absolute sensitivites. A linear algebraic characterization of the matrix of absolute sensitivities for quasi-thermostatic CRN is derived via a Cramer-Rao bound for CRN, which is based on the the analogy between quasi-thermostatic steady states and the exponential family of probability distributions.
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化学反应网络中的克拉默-拉奥约束和绝对灵敏度
化学反应网络(CRN)是理解生物功能的一类重要模型,如细胞信息处理、新陈代谢途径的稳健性和控制、昼夜节律等。然而,任何描述某种功能的 CRN 都不是孤立的,而是一个更大网络的一部分,因此会不断受到外部变化的影响。在[Shinar、Alon 和 Feinberg。"化学反应网络的敏感性和鲁棒性"。SIAM J App Math (2009):977-998.] 中,研究了 CRN 对线性守恒量变化的响应,称为敏感性,并提出了如何构建绝对敏感性(即与基础无关的敏感性)的问题。本文通过应用信息几何方法,提供了这样一种构造。我们的想法是追踪特定化学物质的浓度变化如何传播到稳态中所有其他化学物质的变化。这在绝对敏感度矩阵中进行了编码。根据准恒温稳态与概率分布指数族之间的类比关系,通过 CRN 的 Cramer-Raobound 得出了准恒温 CRN 绝对敏感度矩阵的线性代数特征。
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