title: An efficient finite-difference strategy for sensitivity analysis of stochastic models of biochemical systems.
abstract: 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.
authors.affiliation: Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada. Electronic address: monjur.morshed@uwaterloo.ca.
authors.forename: Monjur
authors.initials: M
authors.lastname: Morshed
authors.affiliation: Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada. Electronic address: bingalls@uwaterloo.ca.
authors.forename: Brian
authors.initials: B
authors.lastname: Ingalls
authors.affiliation: Department of Mathematics, Ryerson University, Toronto, Ontario M5B 2K3, Canada. Electronic address: silvana@ryerson.ca.
authors.forename: Silvana
authors.initials: S
authors.lastname: Ilie
mesh_terms: D000465:Algorithms; D001669:Biochemical Phenomena / Q000502:physiology*; D002468:Cell Physiological Phenomena / Q000502:physiology*; D003198:Computer Simulation; D007700:Kinetics; D008954:Models, Biological; D008956:Models, Chemical; D008957:Models, Genetic; D013269:Stochastic Processes
keywords: Adaptive time-stepping; Chemical Master Equation; Sensitivity analysis; Stochastic models of biochemical kinetics; Stochastic simulation algorithm; tau-Leaping method