Cramer-Rao bound and absolute sensitivity in chemical reaction networks

Fuente: arXiv
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Autores principales: Loutchko, Dimitri, Sughiyama, Yuki, Kobayashi, Tetsuya J.
Formato: Preprint
Publicado: 2024
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author Loutchko, Dimitri
Sughiyama, Yuki
Kobayashi, Tetsuya J.
author_facet Loutchko, Dimitri
Sughiyama, Yuki
Kobayashi, Tetsuya J.
contents 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 concentrations within a steady state. This is encoded in the matrix of absolute sensitivities. As the main technical tool, a multivariate Cramer-Rao bound for CRN is proven, which is based on the the analogy between quasi-thermostatic steady states and the exponential family of probability distributions. This leads to a linear algebraic characterization of the matrix of absolute sensitivities for quasi-thermostatic CRN. As an example, the core module of the IDHKP-IDH glyoxylate bypass regulation system is analyzed analytically and numerically by extensive random sampling of the concentration space. The experimentally known findings for the robustness of the IDH enzyme are confirmed and a hidden symmetry at the level of distributions is revealed, providing a blueprint for the analysis of the robustness properties of CRNs.
format Preprint
id arxiv_https___arxiv_org_abs_2401_06987
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Cramer-Rao bound and absolute sensitivity in chemical reaction networks
Loutchko, Dimitri
Sughiyama, Yuki
Kobayashi, Tetsuya J.
Molecular Networks
Information Theory
Biological Physics
Chemical Physics
80A30, 37C05, 37C25, 92C45, 53B12, 53B50, 62B11, 14M25
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 concentrations within a steady state. This is encoded in the matrix of absolute sensitivities. As the main technical tool, a multivariate Cramer-Rao bound for CRN is proven, which is based on the the analogy between quasi-thermostatic steady states and the exponential family of probability distributions. This leads to a linear algebraic characterization of the matrix of absolute sensitivities for quasi-thermostatic CRN. As an example, the core module of the IDHKP-IDH glyoxylate bypass regulation system is analyzed analytically and numerically by extensive random sampling of the concentration space. The experimentally known findings for the robustness of the IDH enzyme are confirmed and a hidden symmetry at the level of distributions is revealed, providing a blueprint for the analysis of the robustness properties of CRNs.
title Cramer-Rao bound and absolute sensitivity in chemical reaction networks
topic Molecular Networks
Information Theory
Biological Physics
Chemical Physics
80A30, 37C05, 37C25, 92C45, 53B12, 53B50, 62B11, 14M25
url https://arxiv.org/abs/2401.06987