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.
Long-term behaviors of biochemical reaction networks (BRNs) are described by steady states in deterministic models and stationary distributions in stochastic models. Unlike deterministic steady states, stationary distributions capturing inherent fluctuations of reactions are extremely difficult to derive analytically due to the curse of dimensionality. Here, we develop a method to derive analytic stationary distributions from deterministic steady states by transforming BRNs to have a special dynamic property, called complex balancing. Specifically, we merge nodes and edges of BRNs to match in- and out-flows of each node. This allows us to derive the stationary distributions of a large class of BRNs, including autophosphorylation networks of EGFR, PAK1, and Aurora B kinase and a genetic toggle switch. This reveals the unique properties of their stochastic dynamics such as robustness, sensitivity, and multi-modality. Importantly, we provide a user-friendly computational package, CASTANET, that automatically derives symbolic expressions of the stationary distributions of BRNs to understand their long-term stochasticity.
more » « less- Award ID(s):
- 1849588
- NSF-PAR ID:
- 10230469
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Communications Biology
- Volume:
- 4
- Issue:
- 1
- ISSN:
- 2399-3642
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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