Modeling delay in genetic networks: From delay birth-death processes to delay stochastic differential equations

Abstract

Delay is an important and ubiquitous aspect of many biochemical processes. For example, delay plays a central role in the dynamics of genetic regulatory networks as it stems from the sequential assembly of first mRNA and then protein. Genetic regulatory networks are therefore frequently modeled as stochastic birth-death processes with delay. Here we examine the relationship between delay birth-death processes and their appropriate approximating delay chemical Langevin equations. We prove that the distance between these two descriptions, as measured by expectations of functionals of the processes, converges to zero with increasing system size. Further, we prove that the delay birth-death process converges to the thermodynamic limit as system size tends to infinity. Our results hold for both fixed delay and distributed delay. Simulations demonstrate that the delay chemical Langevin approximation is accurate even at moderate system sizes. It captures dynamical features such as the spatial and temporal distributions of transition pathways in metastable systems, oscillatory behavior in negative feedback circuits, and cross-correlations between nodes in a network. Overall, these results provide a foundation for using delay stochastic differential equations to approximate the dynamics of birth-death processes with delay.