Improved estimations of stochastic chemical kinetics by finite state expansion

Quantitative mechanistic models based on reaction networks with stochastic chemical kinetics can help elucidate fundamental biological process where random fluctuations are relevant, such as in single cells. The dynamics of such models is described by the master equation, which provides the time course evolution of the probability distribution across the discrete state space consisting of vectors of population levels of the interacting biochemical species. Since solving the master equation exactly is very difficult in general due to the combinatorial explosion of the state space size, several analytical approximations have been proposed. The deterministic rate equation (DRE) offers a macroscopic view of the system by means of a system of differential equations that estimate the average populations for each species, but it may be inaccurate in the case of nonlinear interactions such as in mass-action kinetics. Here we propose finite state expansion (FSE), an analytical method that mediates between the microscopic and the macroscopic interpretations of a chemical reaction network by coupling the master equation dynamics of a chosen subset of the discrete state space with the population dynamics of the DRE. This is done via an algorithmic translation of a chemical reaction network into a target expanded one where each discrete state is represented as a further distinct chemical species. The translation produces a network with stochastically equivalent dynamics, but the DRE of the expanded network can be interpreted as a correction to the original ones. Through a publicly available software implementation of FSE, we demonstrate its effectiveness in models from systems biology which challenge state-of-the-art techniques due to the presence of intrinsic noise, multi-scale population dynamics, and multi-stability.