Control-based continuation: a new approach to prototype synthetic gene networks
Control-based continuation: a new approach to prototype synthetic gene networks
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基于控制的延续：原型合成基因网络的新方法
DOI：
10.1101/2021.12.21.473142
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
De Cesare I
中科院分区：
文献类型：
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作者：
De Cesare I
基于控制的延拓（CBC）方法是进行物理实验分岔分析的一种通用而系统的方法。CBC不依赖于数学模型，因此克服了通过建模和参数估计间接识别分叉曲线时引入的不确定性。我们证明，在硅片上，CBC的适用性，生化过程跟踪平衡曲线的拨动开关，其中包括加性过程噪声和表现出双稳态。我们比较CBC使用无模型和基于模型的控制策略时得到的结果，并表明两者都可以跟踪稳定和不稳定的解决方案，揭示双稳态。然后，我们证明CBC的条件下更有代表性的anin vivoexperiment使用基于代理的模拟器描述细胞生长和分裂，细胞间的变异性，空间分布和扩散的化学品。我们进一步展示了如何识别曲线可用于参数估计，并讨论CBC如何显着加速合成基因调控网络的原型。
Control-Based Continuation (CBC) is a general and systematic method to carry out the bifurcation analysis of physical experiments. CBC does not rely on a mathematical model and thus overcomes the uncertainty introduced when identifying bifurcation curves indirectly through modeling and parameter estimation. We demonstrate,in silico, CBC applicability to biochemical processes by tracking the equilibrium curve of a toggle switch, which includes additive process noise and exhibits bistability. We compare the results obtained when CBC uses a model-free and model-based control strategy and show that both can track stable and unstable solutions, revealing bistability. We then demonstrate CBC in conditions more representative of anin vivoexperiment using an agent-based simulator describing cell growth and division, cell-to-cell variability, spatial distribution, and diffusion of chemicals. We further show how the identified curves can be used for parameter estimation and discuss how CBC can significantly accelerate the prototyping of synthetic gene regulatory networks.