Metastable behavior in Markov processes with internal states

DOI10.1007/S00285-013-0723-1MaRDI QIDQ464782zbMATH OpenOpenAlexWikidataFDO

Authors Jon Chapman, Jay M. Newby

Publication date 30 October 2014

Published in Journal of Mathematical Biology (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1304.6957

zbMATH Keywords

large deviationgene expressionperturbation theorymetastabilityrare eventsjump processproteininternal statesmean first exit timeWKB methods

Mathematics Subject Classification ID

Large deviations (60F10) Protein sequences, DNA sequences (92D20) Singular perturbations, turning point theory, WKB methods for ordinary differential equations (34E20)

Abstract: A perturbation framework is developed to analyze metastable behavior in stochastic processes with random internal and external states. The process is assumed to be under weak noise conditions, and the case where the deterministic limit is bistable is considered. A general analytical approximation is derived for the stationary probability density and the mean switching time between metastable states, which includes the pre exponential factor. The results are illustrated with a model of gene expression that displays bistable switching. In this model, the external state represents the number of protein molecules produced by a hypothetical gene. Once produced, a protein is eventually degraded. The internal state represents the activated or unactivated state of the gene; in the activated state the gene produces protein more rapidly than the unactivated state. The gene is activated by a dimer of the protein it produces so that the activation rate depends on the current protein level. This is a well studied model, and several model reductions and diffusion approximation methods are available to analyze its behavior. However, it is unclear if these methods accurately approximate long-time metastable behavior (i.e., mean switching time between metastable states of the bistable system). Diffusion approximations are generally known to fail in this regard.

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Cited in

(11)

• Heavy-tailed distributions in a stochastic gene autoregulation model
• Exact and WKB-approximate distributions in a gene expression model with feedback in burst frequency, burst size, and protein stability
• Stochastic switching in biology: from genotype to phenotype
• Stationary and time-dependent molecular distributions in slow-fast feedback circuits
• Fluctuating-rate model with multiple gene states
• Metastability of exponentially perturbed Markov chains
• Noise induced escape in one-population and two-population stochastic neural networks with internal states
• Mixture distributions in a stochastic gene expression model with delayed feedback: a WKB approximation approach
• Extreme first passage times for populations of identical rare events
• Postponing production exponentially enhances the molecular memory of a stochastic switch
• On the Hamiltonian structure of large deviations in stochastic hybrid systems

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