Exploring the Dynamics of Nonlinear Biochemical Systems using Control-Based Continuation

Exploring the Dynamics of Nonlinear Biochemical Systems using Control-Based Continuation
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使用基于控制的延拓探索非线性生化系统的动力学

DOI:
10.1101/695866
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发表时间:
2019
期刊:
--
影响因子:
--
通讯作者:
Gomes B
Gomes B
中科院分区:
--
文献类型:
--
作者:
Gomes B

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摘要数学建模在系统生物学中经常被用来理解引起基因表达中的非线性现象的机制,如开关行为和时间振荡。模型预测和分叉分析的可靠性依赖于建模假设和模型参数的具体选择;然而,由于实验数据中生化相互作用和噪声的复杂性,模型的辨识具有很高的挑战性。基于控制的连续(CBC)方法是一种在实验测试期间直接利用反馈控制和路径跟踪算法来探索非线性物理系统的动态特性的方法。到目前为止,CBC的应用仅限于非生物(即机电)系统。本文数值研究了CBC用于跟踪生化系统的动态特性,特别是调节胚胎干细胞多能性的基因的双稳态动力学。用一个微分方程模型来模拟潜在的监管网络动态。我们的结果为利用CBC和外部反馈控制平台跟踪对细胞决策至关重要的基因的开关状动态变化的创新方法铺平了道路。
AbstractMathematical modelling is routinely used in Systems Biology to understand the mechanisms causing nonlinear phenomena in gene expression, such as switch-like behaviours and temporal oscillations. The reliability of model predictions and bifurcation analysis depend on modelling assumptions and specific choices of model parameters; however, the identification of models is highly challenging due to the complexity of biochemical interactions and noise in experimental data.Control-Based Continuation (CBC) is a method that exploits feedback control and path following algorithms to explore the dynamic features of a nonlinear physical system directly during experimental tests. CBC applications have so far been limited to non-living (i.e. electro-mechanical) systems.This paper numerically investigates the use of CBC for tracking dynamical features of biochemical systems and, in particular, the bistable dynamics of a gene regulating pluripotency in embryonic stem cells. A differential equation model is used to simulate the underlying regulatory network dynamics. Our results pave the way for innovative methodologies to track switch-like dynamics of genes important for cell decision making using CBC and external feedback control platforms.
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