Stochastic analysis of a miRNA-protein toggle switch

TL;DR

This paper investigates the stochastic behavior of a miRNA-protein toggle switch in cell cycle regulation, comparing stochastic and deterministic models to understand their agreement and differences in biological systems.

Contribution

It introduces a simplified analytical model and numerical simulations to analyze stochastic effects in a biochemical circuit, highlighting conditions where stochastic and deterministic models diverge.

Findings

Optimal agreement between models in many parameters

Differences near monostable-bistable transition points

Stochastic effects can mask bistability in the distribution tails

Abstract

Within systems biology there is an increasing interest in the stochastic behavior of genetic and biochemical reaction networks. An appropriate stochastic description is provided by the chemical master equation, which represents a continuous time Markov chain (CTMC). In this paper we consider the stochastic properties of a biochemical circuit, known to control eukaryotic cell cycle and possibly involved in oncogenesis, recently proposed in the literature within a deterministic framework. Due to the inherent stochasticity of biochemical processes and the small number of molecules involved, the stochastic approach should be more correct in describing the real system: we study the agreement between the two approaches by exploring the system parameter space. We address the problem by proposing a simplified version of the model that allows analytical treatment, and by performing numerical simulations for the full model. We observed optimal agreement between the stochastic and the deterministic description of the circuit in a large range of parameters, but some substantial differences arise in at least two cases: 1) when the deterministic system is in the proximity of a transition from a monostable to a bistable configuration, and 2) when bistability (in the deterministic system) is "masked" in the stochastic system by the distribution tails. The approach provides interesting estimates of the optimal number of molecules involved in the toggle. Our discussion of the points of strengths, potentiality and weakness of the chemical master equation in systems biology and the differences with respect to deterministic modeling are leveraged in order to provide useful advice for both the bioinformatician practitioner and the theoretical scientist.