Validity conditions for moment closure approximations in stochastic chemical kinetics

TL;DR

This paper investigates the conditions under which moment-closure approximations accurately reflect the stochastic dynamics of chemical systems, highlighting their limitations and validity ranges based on molecule numbers.

Contribution

It provides a systematic analysis of the validity conditions for moment-closure methods in stochastic chemical kinetics, clarifying when these approximations are reliable.

Findings

MA equations are valid only within specific molecule number ranges.

Outside these ranges, MA can produce unphysical or incorrect results.

Comparison with higher-order solutions is necessary to ensure accuracy.

Abstract

Approximations based on moment-closure (MA) are commonly used to obtain estimates of the mean molecule numbers and of the variance of fluctuations in the number of molecules of chemical systems. The advantage of this approach is that it can be far less computationally expensive than exact stochastic simulations of the chemical master equation. Here we numerically study the conditions under which the MA equations yield results reflecting the true stochastic dynamics of the system. We show that for bistable and oscillatory chemical systems with deterministic initial conditions, the solution of the MA equations can be interpreted as a valid approximation to the true moments of the CME, only when the steady-state mean molecule numbers obtained from the chemical master equation fall within a certain finite range. The same validity criterion for monostable systems implies that the steady-state mean molecule numbers obtained from the chemical master equation must be above a certain threshold. For mean molecule numbers outside of this range of validity, the MA equations lead to either qualitatively wrong oscillatory dynamics or to unphysical predictions such as negative variances in the molecule numbers or multiple steady-state moments of the stationary distribution as the initial conditions are varied. Our results clarify the range of validity of the MA approach and show that pitfalls in the interpretation of the results can only be overcome through the systematic comparison of the solutions of the MA equations of a certain order with those of higher orders.