Stochastic Hazard Analysis of Genetic Circuits in iBioSim and STAMINA

ACS Synth Biol. 2021 Oct 15;10(10):2532-2540. doi: 10.1021/acssynbio.1c00159. Epub 2021 Oct 4.

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.

Keywords: genetic circuits; genetic regulatory networks; hazards and glitches; model verification; stochastic simulation; synthetic biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biosensing Techniques
  • Gene Regulatory Networks*
  • Models, Theoretical
  • Probability
  • Stochastic Processes
  • Synthetic Biology / methods*