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Reduction of dynamical biochemical reactions networks in computational biology

机译:减少计算生物学中动态生化反应网络

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摘要

Biochemical networks are used in computational biology, to model mechanistic details of systems involved in cell signaling, metabolism, and regulation of gene expression. Parametric and structural uncertainty, as well as combinatorial explosion are strong obstacles against analyzing the dynamics of large models of this type. Multiscaleness, an important property of these networks, can be used to get past some of these obstacles. Networks with many well separated time scales, can be reduced to simpler models, in a way that depends only on the orders of magnitude and not on the exact values of the kinetic parameters. The main idea used for such robust simplifications of networks is the concept of dominance among model elements, allowing hierarchical organization of these elements according to their effects on the network dynamics. This concept finds a natural formulation in tropical geometry. We revisit, in the light of these new ideas, the main approaches to model reduction of reaction networks, such as quasi-steady state (QSS) and quasi-equilibrium approximations (QE), and provide practical recipes for model reduction of linear and non-linear networks. We also discuss the application of model reduction to the problem of parameter identification, via backward pruning machine learning techniques.
机译:生化网络用于计算生物学,以对涉及细胞信号传导,代谢和基因表达调控的系统的机械细节进行建模。参数和结构不确定性以及组合爆炸是阻碍分析此类大型模型动力学的强大障碍。多尺度性是这些网络的重要属性,可以用来克服这些障碍中的一些障碍。具有许多时间间隔很好的网络可以简化为更简单的模型,其方式仅取决于数量级,而不取决于动力学参数的确切值。用于网络的这种鲁棒简化的主要思想是模型元素之间的支配性概念,允许根据这些元素对网络动力学的影响进行分层组织。这个概念在热带几何中找到了自然的配方。根据这些新思想,我们重新研究了反应网络模型简化的主要方法,如准稳态(QSS)和拟均衡近似(QE),并提供了线性和非线性模型简化的实用方法-线性网络。我们还将讨论通过向后修剪机器学习技术将模型归约应用于参数识别问题。

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