Noise-induced transitions in gene circuits: a perturbative approach for slow noise

TL;DR

This paper introduces a perturbative approach to analyze how slow, nonlinear extrinsic noise causes gene circuits, like toggle switches, to undergo noise-induced transitions, leading to bimodal behavior in certain parameter regimes.

Contribution

The authors develop a novel perturbative methodology for slow noise with finite correlation time, improving predictions of noise-induced transitions in gene circuits beyond previous methods.

Findings

Noise causes toggle switches to become bimodal in monostable regions.

Higher order corrections improve transition predictions for moderate correlation times.

Noise affects one gene more than the other at intermediate intensities.

Abstract

We consider a generic class of gene circuits affected by nonlinear extrinsic noise. To address this nonlinearity we introduce a general perturbative methodology based on assuming timescale separation between noise and genes dynamics, with fluctuations exhibiting a large but finite correlation time. We apply this methodology to the case of the toggle switch, and by considering biologically relevant log-normal fluctuations, we find that the system exhibits noise-induced transitions. The system becomes bimodal in regions of the parameter space where it would be deterministically monostable. We show that by including higher order corrections our methodology allows one to obtain correct predictions for the occurrence of transitions even for not so large correlation time of the fluctuations, overcoming thereby limitations of previous theoretical approaches. Interestingly we find that at intermediate noise intensities the noise-induced transition in the toggle switch affects one of the genes involved, but not the other one.