An efficient finite-difference strategy for sensitivity analysis of stochastic models of biochemical systems

Sensitivity analysis characterizes the dependence of a model's behaviour on system parameters. It is a critical tool in the formulation, characterization, and verification of models of biochemical reaction networks, for which confident estimates of parameter values are often lacking. In this paper, we propose a novel method for sensitivity analysis of discrete stochastic models of biochemical reaction systems whose dynamics occur over a range of timescales. This method combines finite-difference approximations and adaptive tau-leaping strategies to efficiently estimate parametric sensitivities for stiff stochastic biochemical kinetics models, with negligible loss in accuracy compared with previously published approaches. We analyze several models of interest to illustrate the advantages of our method.