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Abstract Continuous-time Markov chains are frequently used as stochastic models for chemical reaction networks, especially in the growing field of systems biology. A fundamental problem for these Stochastic Chemical Reaction Networks (SCRNs) is to understand the dependence of the stochastic behavior of these systems on the chemical reaction rate parameters. Towards solving this problem, in this paper we develop theoretical tools called comparison theorems that provide stochastic ordering results for SCRNs. These theorems give sufficient conditions for monotonic dependence on parameters in these network models, which allow us to obtain, under suitable conditions, information about transient and steady-state behavior. These theorems exploit structural properties of SCRNs, beyond those of general continuous-time Markov chains. Furthermore, we derive two theorems to compare stationary distributions and mean first passage times for SCRNs with different parameter values, or with the same parameters and different initial conditions. These tools are developed for SCRNs taking values in a generic (finite or countably infinite) state space and can also be applied for non-mass-action kinetics models. When propensity functions are bounded, our method of proof gives an explicit method for coupling two comparable SCRNs, which can be used to simultaneously simulate their sample paths in a comparable manner. We illustrate our results with applications to models of enzymatic kinetics and epigenetic regulation by chromatin modifications.
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Slack reactants: A state-space truncation framework to estimate quantitative behavior of the chemical master equation
State space truncation methods are widely used to approximate solutions of the chemical master equation. While most methods of this kind focus on truncating the state space directly, in this work, we propose modifying the underlying chemical reaction network by introducing slack reactants that indirectly truncate the state space. More specifically, slack reactants introduce an expanded chemical reaction network and impose a truncation scheme based on desired mass conservation laws. This network structure also allows us to prove inheritance of special properties of the original model, such as irreducibility and complex balancing. We use the network structure imposed by slack reactants to prove the convergence of the stationary distribution and first arrival times. We then provide examples comparing our method with the stationary finite state projection and finite buffer methods. Our slack reactant system appears to be more robust than some competing methods with respect to calculating first arrival times.
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- Award ID(s):
- 1763272
- PAR ID:
- 10593508
- Publisher / Repository:
- American Institute of Physics
- Date Published:
- Journal Name:
- The Journal of Chemical Physics
- Volume:
- 153
- Issue:
- 5
- ISSN:
- 0021-9606
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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