Dichotomous noise models of gene switches

Abstract

Molecular noise in gene regulatory networks has two intrinsic components, one part being due to fluctuations caused by the birth and death of protein or mRNA molecules which are often present in small numbers and the other part arising from gene state switching, a single molecule event. Stochastic dynamics of gene regulatory circuits appears to be largely responsible for bifurcations into a set of multi-attractor states that encode different cell phenotypes. The interplay of dichotomous single molecule gene noise with the nonlinear architecture of genetic networks generates rich and complex phenomena. In this paper we elaborate on an approximate framework that leads to simple hybrid multi-scale schemes well suited for the quantitative exploration of the steady state properties of large-scale cellular genetic circuits.Through a path sum based analysis of trajectory statistics we elucidate the connection of these hybrid schemes to the underlying master equation and provide a rigorous justification for using dichotomous noise based models to study genetic networks. Numerical simulations of circuit models reveal that the contribution of the genetic noise of single molecule origin to the total noise is significant for a wide range of kinetic regimes.

References in corpus (4)

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• Bistable switching asymptotics for the self regulating gene
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Cited by in corpus (8)

• Intrinsic noise in systems with switching environments
• Inferring gene regulatory networks from single-cell data: a mechanistic approach
• Single-cell stochastic gene expression kinetics with coupled positive-plus-negative feedback
• A stochastic and dynamical view of pluripotency in mouse embryonic stem cells
• Relaxation rates of gene expression kinetics reveal the feedback signs of autoregulatory gene networks
• Model reduction methods for classical stochastic systems with fast-switching environments: reduced master equations, stochastic differential equations, and applications
• Diffusion caused by two noises-active and thermal
• Synchronization transition in the two-dimensional Kuramoto model with dichotomous noise