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A measure of concentration robustness in a biochemical reaction network and its application on system identification

机译:生化反应网络中浓度稳健性的度量及其在系统识别中的应用

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Variations in the concentrations of biomolecular species in vivo are inevitable, but regulation systems will act to maintain concentrations of certain species within proper levels. Such a ubiquitous trait in biological systems is the so-called concentration robustness. In this work, we study the concentration robustness of glycerol metabolism system, in which some mechanistic details are not clearly known and the true metabolic system need to be identified from all possible ones. We give a quantitative index to measure the concentration robustness of the considered system, which is characterized as the maximum relative variation in certain entries of steady state caused by the perturbations of operating parameters. Based on the proposed robustness index, a minimax dynamic optimization problem is developed for identifying the kinetic parameters as well as the unknown metabolic mechanisms. A scheme based on Monte-Carlo method is proposed to evaluate the robustness index approximately and convergence result is obtained. An algorithm is constructed to solve the dynamic optimization problem and numerical results are presented to show that the proposed robustness index could measure concentration robustness of the considered system properly.
机译:体内生物分子种类的浓度变化是不可避免的,但是调节系统将起到将某些种类的浓度保持在适当水平的作用。生物系统中这种普遍存在的特性就是所谓的浓度稳健性。在这项工作中,我们研究了甘油代谢系统的浓度稳健性,其中尚不清楚某些机理细节,需要从所有可能的机理中识别出真正的代谢系统。我们给出一个定量指标来衡量所考虑系统的浓度稳健性,其特征是由运行参数的扰动引起的某些稳态输入项的最大相对变化。基于提出的鲁棒性指标,开发了一个极大极小动态优化问题,用于识别动力学参数以及未知的代谢机制。提出了一种基于蒙特卡洛方法的鲁棒性指标评估方案,并获得了收敛结果。构造了求解动态优化问题的算法,数值结果表明所提出的鲁棒性指标可以正确地衡量所考虑系统的浓度鲁棒性。

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