Efficient calculation of steady state probability distribution for stochastic biochemical reaction network

Shahriar Karim, Gregery T Buzzard, David M Umulis

The Steady State (SS) probability distribution is an important quantity needed to characterize the steady state behavior of many stochastic biochemical networks. In this paper, we propose an efficient and accurate approach to calculating an approximate SS probability distribution from solution of the Chemical Master Equation (CME) under the assumption of the existence of a unique deterministic SS of the system. To find the approximate solution to the CME, a truncated state-space representation is used to reduce the state-space of the system and translate it to a finite dimension. The subsequent ill-posed eigenvalue problem of a linear system for the finite state-space can be converted to a well-posed system of linear equations and solved. The proposed strategy yields efficient and accurate estimation of noise in stochastic biochemical systems. To demonstrate the approach, we applied the method to characterize the noise behavior of a set of biochemical networks of ligand-receptor interactions for Bone Morphogenetic Protein (BMP) signaling. We found that recruitment of type II receptors during the receptor oligomerization by itself doesn't not tend to lower noise in receptor signaling, but regulation by a secreted co-factor may provide a substantial improvement in signaling relative to noise. The steady state probability approximation method shortened the time necessary to calculate the probability distributions compared to earlier approaches, such as Gillespie's Stochastic Simulation Algorithm (SSA) while maintaining high accuracy.