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首页> 外文期刊>Computational Biology and Bioinformatics, IEEE/ACM Transactions on >Quantifying Dynamic Stability of Genetic Memory Circuits
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Quantifying Dynamic Stability of Genetic Memory Circuits

机译：量化遗传记忆电路的动态稳定性

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摘要

Bistability/Multistability has been found in many biological systems including genetic memory circuits. Proper characterization of system stability helps to understand biological functions and has potential applications in fields such as synthetic biology. Existing methods of analyzing bistability are either qualitative or in a static way. Assuming the circuit is in a steady state, the latter can only reveal the susceptibility of the stability to injected DC noises. However, this can be inappropriate and inadequate as dynamics are crucial for many biological networks. In this paper, we quantitatively characterize the dynamic stability of a genetic conditional memory circuit by developing new dynamic noise margin (DNM) concepts and associated algorithms based on system theory. Taking into account the duration of the noisy perturbation, the DNMs are more general cases of their static counterparts. Using our techniques, we analyze the noise immunity of the memory circuit and derive insights on dynamic hold and write operations. Considering cell-to-cell variations, our parametric analysis reveals that the dynamic stability of the memory circuit has significantly varying sensitivities to underlying biochemical reactions attributable to differences in structure, time scales, and nonlinear interactions between reactions. With proper extensions, our techniques are broadly applicable to other multistable biological systems.
机译：在包括遗传记忆电路的许多生物系统中已经发现了双稳态/多稳定性。正确表征系统稳定性有助于理解生物学功能，并在合成生物学等领域具有潜在的应用。分析双稳态的现有方法是定性的或静态的。假设电路处于稳定状态，则后者只能显示出稳定性对于注入的直流噪声的敏感性。但是，这可能是不适当的，因为动力学对于许多生物网络至关重要。在本文中，我们通过基于系统理论开发新的动态噪声容限（DNM）概念和相关算法，定量地描述了遗传条件存储电路的动态稳定性。考虑到噪声扰动的持续时间，DNM是其静态对应物的更一般情况。使用我们的技术，我们分析了存储电路的抗扰性，并获得了有关动态保持和写入操作的见解。考虑到细胞之间的差异，我们的参数分析表明，存储电路的动态稳定性对潜在的生化反应的敏感性有显着变化，这归因于结构，时间尺度以及反应之间的非线性相互作用。通过适当的扩展，我们的技术可广泛应用于其他多稳态生物系统。

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