Differential equation models of biochemical networks are frequently associated with a large degree of uncertainty in parameters and/or initial conditions. However, estimating the impact of this uncertainty on model predictions via Monte Carlo simulation is computationally demanding. A more efficient approach could be to track a system of low-order statistical moments of the state. Unfortunately, when the underlying model is nonlinear, the system of moment equations is infinite-dimensional and cannot be solved without a moment closure approximation which may introduce bias in the moment dynamics. Here, we present a new method to study the time evolution of the desired moments for nonlinear systems with polynomial rate laws. Our approach is based on solving a system of low-order moment equations by substituting the higher-order moments with Monte Carlo-based estimates from a small number of simulations, and using an extended Kalman filter to counteract Monte Carlo noise. Our algorithm provides more accurate and robust results compared to traditional Monte Carlo and moment closure techniques, and we expect that it will be widely useful for the quantification of uncertainty in biochemical model predictions.
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