Stochastic Hazard Analysis of Genetic Circuits in iBioSim and STAMINA
Stochastic Hazard Analysis of Genetic Circuits in iBioSim and STAMINA
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iBioSim 和 STAMINA 中遗传电路的随机危害分析
DOI：
10.1021/acssynbio.1c00159
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发表时间：
2021
影响因子：
4.7
通讯作者：
Myers, Chris J.
中科院分区：
文献类型：
--
作者：
Buecherl, Lukas;Roberts, Riley;Fontanarrosa, Pedro;Thomas, Payton J.;Mante, Jeanet;Zhang, Zhen;Myers, Chris J.
在合成生物学中，组合电路被用于为各种新应用程序（如生物传感器，药物输送系统和生物燃料）编程细胞。与异步电子电路类似，一些组合遗传电路可能会显示由多个输入变化引起的不必要的开关变化（毛刺）。根据生物回路的不同，小故障可能会导致不可逆的影响，并危及回路的功能。本文提出了一种随机分析，预测故障倾向的三个实现的遗传电路与已知的故障行为。分析使用STostochastic近似模型检查器的无限状态分析（STAMINA），随机验证的工具。通过与iBioSim中的随机模拟进行比较，验证了STAMINA结果，从而进一步改进了STAMINA。本文表明，随机验证可以利用遗传设计师来评估设计选择和输入限制，以达到预期的操作可靠性。
In synthetic biology, combinational circuits are used to program cells for various new applications like biosensors, drug delivery systems, and biofuels. Similar to asynchronous electronic circuits, some combinational genetic circuits may show unwanted switching variations (glitches) caused by multiple input changes. Depending on the biological circuit, glitches can cause irreversible effects and jeopardize the circuit’s functionality. This paper presents a stochastic analysis to predict glitch propensities for three implementations of a genetic circuit with known glitching behavior. The analysis usesSTochastic Approximate Model-checker for INfinite-state Analysis(STAMINA), a tool for stochastic verification. The STAMINA results were validated by comparison to stochastic simulation in iBioSim resulting in further improvements of STAMINA. This paper demonstrates that stochastic verification can be utilized by genetic designers to evaluate design choices and input restrictions to achieve a desired reliability of operation.