Stochastic Hazard Analysis of Genetic Circuits in iBioSim and STAMINA
ACS Synthetic Biology
American Chemical Society
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 uses STochastic 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.
Lukas Buecherl, Riley Roberts, Pedro Fontanarrosa, Payton J. Thomas, Jeanet Mante, Zhen Zhang, and Chris J. Myers ACS Synthetic Biology 2021 10 (10), 2532-2540 DOI: 10.1021/acssynbio.1c00159