Sensitivity Analysis for Multiscale Stochastic Reaction Networks Using Hybrid Approximations

Bull Math Biol. 2019 Aug;81(8):3121-3158. doi: 10.1007/s11538-018-0521-4. Epub 2018 Oct 9.

Abstract

We consider the problem of estimating parameter sensitivities for stochastic models of multiscale reaction networks. These sensitivity values are important for model analysis, and the methods that currently exist for sensitivity estimation mostly rely on simulations of the stochastic dynamics. This is problematic because these simulations become computationally infeasible for multiscale networks due to reactions firing at several different timescales. However it is often possible to exploit the multiscale property to derive a "model reduction" and approximate the dynamics as a Piecewise deterministic Markov process, which is a hybrid process consisting of both discrete and continuous components. The aim of this paper is to show that such PDMP approximations can be used to accurately and efficiently estimate the parameter sensitivity for the original multiscale stochastic model. We prove the convergence of the original sensitivity to the corresponding PDMP sensitivity, in the limit where the PDMP approximation becomes exact. Moreover, we establish a representation of the PDMP parameter sensitivity that separates the contributions of discrete and continuous components in the dynamics and allows one to efficiently estimate both contributions.

Keywords: Coupling; Multiscale networks; Parameter sensitivity; Piecewise deterministic Markov processes; Random time change representation; Reduced models; Stochastic reaction networks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Biochemical Phenomena
  • Computer Simulation
  • Enzymes / metabolism
  • Gene Expression
  • Gene Regulatory Networks
  • Kinetics
  • Markov Chains
  • Mathematical Concepts
  • Models, Biological*
  • Poisson Distribution
  • Stochastic Processes
  • Systems Biology

Substances

  • Enzymes