Title

Stochastic Hazard Analysis of Genetic Circuits in iBioSim and STAMINA

Document Type

Article

Journal/Book Title/Conference

ACS Synthetic Biology

Volume

10

Issue

10

Publisher

American Chemical Society

Publication Date

10-4-2021

Funder

NSF

First Page

2532

Last Page

2540

Abstract

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.

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