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Biophys. J. BioFAST: First Published February 4, 2005. doi:10.1529/biophysj.104.053405
© 2005 by the Biophysical Society.

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BIOPHYSICAL THEORY AND MODELING

Sensitivity Analysis of Discrete Stochastic Systems

Rudiyanto Gunawan 1, Yang Cao 1, Linda Petzold 1 and Francis Doyle 1*

1 UCSB

* To whom correspondence should be addressed. E-mail: doyle{at}engineering.ucsb.edu.

Submitted on September 22, 2004
Revised on November 4, 2004
Accepted on 21 January 2005


  Abstract
Sensitivity analysis quantifies the dependence of system "behavior" on the parameters that affect the process dynamics. Classical sensitivity analysis, however, does not directly apply to discrete stochastic dynamical systems, which have recently gained popularity because of its relevance to biological processes. In this work, the sensitivity analysis for discrete stochastic processes is developed based on density function (distribution) sensitivity, using an analog of the classical sensitivity and the Fisher Information Matrix. There exist many circumstances, such as in systems with multistability, in which the stochastic effects become nontrivial and classical sensitivity analysis on deterministic representation of the system cannot adequately capture the true system behavior. The proposed analysis is applied to a bistable chemical system - the Schloegl model (Gillespie, 1992), and to a synthetic genetic toggle switch model (Gardner et al., 2000). Comparisons between the stochastic and deterministic analysis show the significance of explicit consideration of the probabilistic nature in the sensitivity analysis for this class of processes.

Key Words: biological noise, chemical master equation, gene switch, parameter sensitivity, regulation, stochastic systems




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Copyright © 2005 by the Biophysical Society.