Genetic Circuit Dynamics: Hazard and Glitch Analysis.,ACS Synthetic Biology

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Genetic Circuit Dynamics: Hazard and Glitch Analysis.
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-08-05 , DOI: 10.1021/acssynbio.0c00055
Pedro Fontanarrosa ₁ , Hamid Doosthosseini ₂ , Amin Espah Borujeni _{3,

4} , Yuval Dorfan _{3,

4,

5} , Christopher A Voigt ₄ , Chris Myers ₆

Affiliation

Multiple input changes can cause unwanted switching variations, or glitches, in the output of genetic combinational circuits. These glitches can have drastic effects if the output of the circuit causes irreversible changes within or with other cells such as a cascade of responses, apoptosis, or the release of a pharmaceutical in an off-target tissue. Therefore, avoiding unwanted variation of a circuit’s output can be crucial for the safe operation of a genetic circuit. This paper investigates what causes unwanted switching variations in combinational genetic circuits using hazard analysis and a new dynamic model generator. The analysis is done in previously built and modeled genetic circuits with known glitching behavior. The dynamic models generated not only predict the same steady states as previous models but can also predict the unwanted switching variations that have been observed experimentally. Multiple input changes may cause glitches due to propagation delays within the circuit. Modifying the circuit’s layout to alter these delays may change the likelihood of certain glitches, but it cannot eliminate the possibility that the glitch may occur. In other words, function hazards cannot be eliminated. Instead, they must be avoided by restricting the allowed input changes to the system. Logic hazards, on the other hand, can be avoided using hazard-free logic synthesis. This paper demonstrates this by showing how a circuit designed using a popular genetic design automation tool can be redesigned to eliminate logic hazards.

中文翻译：

遗传电路动力学：危险和故障分析。

多个输入变化会导致不必要的开关变化或毛刺，在遗传组合电路的输出中。如果电路的输出导致其他细胞内或与其他细胞发生不可逆转的变化，例如反应级联、细胞凋亡或药物在脱靶组织中释放，这些故障可能会产生严重影响。因此，避免电路输出的不必要变化对于遗传电路的安全运行至关重要。本文使用危险分析和新的动态模型生成器研究了导致组合遗传电路中不需要的开关变化的原因。分析是在先前构建和建模的具有已知故障行为的遗传电路中完成的。生成的动态模型不仅可以预测与先前模型相同的稳态，还可以预测实验观察到的不需要的开关变化。由于电路内的传播延迟，多次输入变化可能会导致毛刺。修改电路布局以改变这些延迟可能会改变某些毛刺的可能性，但不能消除毛刺发生的可能性。换言之，功能危害无法消除。相反，必须通过限制对系统的允许输入更改来避免它们。另一方面，使用无危险逻辑综合可以避免逻辑危险。本文通过展示如何重新设计使用流行的基因设计自动化工具设计的电路以消除逻辑风险来证明这一点。但不能排除故障发生的可能性。换言之，功能危害无法消除。相反，必须通过限制对系统的允许输入更改来避免它们。另一方面，使用无危险逻辑综合可以避免逻辑危险。本文通过展示如何重新设计使用流行的基因设计自动化工具设计的电路以消除逻辑风险来证明这一点。但不能排除故障发生的可能性。换言之，功能危害无法消除。相反，必须通过限制对系统的允许输入更改来避免它们。另一方面，使用无危险逻辑综合可以避免逻辑危险。本文通过展示如何重新设计使用流行的基因设计自动化工具设计的电路以消除逻辑风险来证明这一点。

更新日期：2020-09-20

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