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.
While the moment closure method uses ad-hoc approximations for high order moments to facilitate numerical integration, they can be avoided in some contexts. For the equilibrium distribution, for example, the time-derivative of all moments is equal to zero. This directly yields constraints that have been used for parameter estimation at steady-state @cite_13 and bounding moments of the equilibrium distribution using semi-definite programming @cite_25 @cite_22 @cite_8 . The latter technique of bounding moments has been successfully adapted in the context of transient analysis @cite_1 @cite_30 @cite_24 . We adapt the constraints proposed in these works to improve statistical estimations via stochastic simulation (cf. section ).
@cite_30 @cite_22 @cite_8 @cite_1 @cite_24 @cite_13 @cite_25
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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 Applying the method of moments to the chemical master equation appearing in stochastic chemical kinetics often leads to the so-called closure problem. Recently, several authors showed that this problem can be partially overcome using moment-based semidefinite programs (SDPs). In particular, they showed that moment-based SDPs can be used to calculate rigorous bounds on various descriptions of the stochastic chemical kinetic system’s stationary distribution(s)—for example, mean molecular counts, variances in these counts, and so on. In this paper, we show that these ideas can be extended to the corresponding dynamic problem, calculating time-varying bounds on the same descriptions. The predictive ability of stochastic chemical reactions is currently limited by the lack of closed form solutions to the governing chemical master equation. To overcome this limitation, this letter proposes a computational method capable of predicting mathematically rigorous upper and lower bounds of transient moments for reactions governed by the law of mass action. We first derive an equation that transient moments must satisfy based on the moment equation. Although this equation is underdetermined, we introduce a set of semidefinite constraints known as moment condition to narrow the feasible set of the variables in the equation. Using these conditions, we formulate a semidefinite program that efficiently and rigorously computes the bounds of transient moment dynamics. The proposed method is demonstrated with illustrative numerical examples and is compared with related works to discuss advantages and limitations. where (an)n ENo is some sequence of nonnegative numbers, (Sn),nENo is the sequence of partial sums, S0 = 0, Sn = XflXk, of another sequence (Xk)kEN of i.i.d. random variables, and A c R is a fixed Borel set such as [0,1] or [0, oo). Examples of such convolution series are subordinated distributions (f=0Oan = 1) which arise as distributions of random sums, and harmonic and ordinary renewal measures (a0 = 0, an = 1 n for all n C N in the first, an = 1 for all n C NO in the second case). These examples are in turn essential for the analysis of the large time behaviour of diverse applied models such as branching and queueing processes, they are also of interest in connection with representation theorems such as the Levy representation of infinitely divisible distributions. A traditional approach to such problems is via regular variation: If the underlying random variables are nonnegative we can use Laplace transforms and the related Abelian and Tauberian theorems [see, e.g., Stam (1973) in the context of subordination and Feller (1971, XIV.3) in connection with renewal theory; Embrechts, Maejima, and Omey (1984) is a recent treatment of generalized renewal measures along these lines]. The approach of the present paper is based on the Wiener-Levy-Gel'fand theorem and has occasionally been called the Banach algebra method. In Gruibel (1983) we gave a new variant of this method for the special case of lattice distributions, showing that by using the appropriate Banach algebras of sequences, arbitrarily fine expansions are possible under certain assumptions on the higher-order differences of (P(X1 = n))fnEN. Here we give a corresponding treatment of nonlattice distributions. We restrict ourselves to an analogue of first-order differences and obtain a number of theorems which perhaps are described best as next-term results. To explain this let us consider a special case in more detail.