Stochastic simulation is a widely used method for estimating quantities in models of chemical reaction networks where uncertainty plays a crucial role. However, reducing the statistical uncertainty of the corresponding estimators requires the generation of a large number of simulation runs, which is computationally expensive. To reduce the number of necessary runs, we propose a variance reduction technique based on control variates. We exploit constraints on the statistical moments of the stochastic process to reduce the estimators' variances. We develop an algorithm that selects appropriate control variates in an on-line fashion and demonstrate the efficiency of our approach on several case studies.
Preface to the first edition. Preface to the second edition. Abbreviated references. I. Stochastic variables. II. Random events. III. Stochastic processes. IV. Markov processes. V. The master equation. VI. One-step processes. VII. Chemical reactions. VIII. The Fokker-Planck equation. IX. The Langevin approach. X. The expansion of the master equation. XI. The diffusion type. XII. First-passage problems. XIII. Unstable systems. XIV. Fluctuations in continuous systems. XV. The statistics of jump events. XVI. Stochastic differential equations. XVII. Stochastic behavior of quantum systems. In this paper we present an overview of the field of deterministic approximation of Markov processes, both in discrete and continuous times. We will discuss mean field approximation of discrete time Markov chains and fluid approximation of continuous time Markov chains, considering the cases in which the deterministic limit process lives in continuous time or discrete time. We also consider some more advanced results, especially those relating to the limit stationary behaviour. We assume a knowledge of modelling with Markov chains, but not of more advanced topics in stochastic processes. In the stochastic formulation of chemical reactions, the dynamics of the first M-order moments of the species populations generally do not form a closed system of differential equations, in the sense that the time-derivatives of first M-order moments generally depend on moments of order higher than M. However, for analysis purposes, these dynamics are often made to be closed by approximating the needed derivatives of the first M-order moments by nonlinear functions of the same moments. These functions are called the moment closure functions. Recent results have introduced the technique of derivative-matching, where the moment closure functions are obtained by first assuming that they exhibit a certain separable form, and then matching time derivatives of the exact (not closed) moment equations with that of the approximate (closed) equations for some initial time and set of initial conditions. However, for multi-species reactions these results have been restricted to second order truncations, i.e, M = 2. This paper extends these results by providing explicit formulas to construct moment closure functions for any arbitrary order of truncation M. We show that with increasing M the closed moment equations provide more accurate approximations to the exact moment equations. Striking features of these moment closure functions are that they are independent of the reaction parameters (reaction rates and stoichiometry) and moreover the dependence of higher-order moment on lower order ones is consistent with the population being jointly lognormally distributed. To illustrate the applicability of our results we consider a simple bi-molecular reaction. Moment estimates from a third order truncation are compared with estimates obtained from a large number of Monte Carlo simulations The stochastic dynamical behavior of a well-stirred mixture of N molecular species that chemically interact through M reaction channels is accurately described by the chemical master equation. It is shown here that, whenever two explicit dynamical conditions are satisfied, the microphysical premise from which the chemical master equation is derived leads directly to an approximate time-evolution equation of the Langevin type. This chemical Langevin equation is the same as one studied earlier by Kurtz, in contradistinction to some other earlier proposed forms that assume a deterministic macroscopic evolution law. The novel aspect of the present analysis is that it shows that the accuracy of the equation depends on the satisfaction of certain specific conditions that can change from moment to moment, rather than on a static system size parameter. The derivation affords a new perspective on the origin and magnitude of noise in a chemically reacting system. It also clarifies the connection between the stochas...