Using computational modeling and experimental synthetic perturbations to probe biological circuits.
Using computational modeling and experimental synthetic perturbations to probe biological circuits.
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DOI：
10.1007/978-1-4939-1878-2_12
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Batchelor E
中科院分区：
文献类型：
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作者：
Porter JR;Batchelor E
本章描述了使用合成生物学扰动的计算模型来分析内源生物回路的方法，特别关注信号和代谢途径。我们描述了一种自下而上的方法，其中构建了常微分方程式来模拟感兴趣路径的核心交互作用。然后我们讨论了模拟合成微扰的方法，这些方法可以用来研究自然电路的性质。考虑到建模和实验之间相互作用的重要性，我们接下来描述构建合成扰动以测试计算预测的实验方法。最后，我们提供了一个p53肿瘤抑制通路的案例研究，说明了对核心网络进行建模、在电子计算机中设计信息丰富的合成扰动以及在体内验证预测的过程。
This chapter describes approaches for using computational modeling of synthetic biology perturbations to analyze endogenous biological circuits, with a particular focus on signaling and metabolic pathways. We describe a bottom-up approach in which ordinary differential equations are constructed to model the core interactions of a pathway of interest. We then discuss methods for modeling synthetic perturbations that can be used to investigate properties of the natural circuit. Keeping in mind the importance of the interplay between modeling and experimentation, we next describe experimental methods for constructing synthetic perturbations to test the computational predictions. Finally, we present a case study of the p53 tumor-suppressor pathway, illustrating the process of modeling the core network, designing informative synthetic perturbations in silico, and testing the predictions in vivo.