title: Adaptive hybrid simulations for multiscale stochastic reaction networks.
abstract: The probability distribution describing the state of a Stochastic Reaction Network (SRN) evolves according to the Chemical Master Equation (CME). It is common to estimate its solution using Monte Carlo methods such as the Stochastic Simulation Algorithm (SSA). In many cases, these simulations can take an impractical amount of computational time. Therefore, many methods have been developed that approximate sample paths of the underlying stochastic process and estimate the solution of the CME. A prominent class of these methods include hybrid methods that partition the set of species and the set of reactions into discrete and continuous subsets. Such a partition separates the dynamics into a discrete and a continuous part. Simulating such a stochastic process can be computationally much easier than simulating the exact discrete stochastic process with SSA. Moreover, the quasi-stationary assumption to approximate the dynamics of fast subnetworks can be applied for certain classes of networks. However, as the dynamics of a SRN evolves, these partitions may have to be adapted during the simulation. We develop a hybrid method that approximates the solution of a CME by automatically partitioning the reactions and species sets into discrete and continuous components and applying the quasi-stationary assumption on identifiable fast subnetworks. Our method does not require any user intervention and it adapts to exploit the changing timescale separation between reactions and/or changing magnitudes of copy-numbers of constituent species. We demonstrate the efficiency of the proposed method by considering examples from systems biology and showing that very good approximations to the exact probability distributions can be achieved in significantly less computational time. This is especially the case for systems with oscillatory dynamics, where the system dynamics change considerably throughout the time-period of interest.
authors.affiliation: Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hepp
authors.affiliation: Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, Switzerland.
authors.forename: Ankit
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, Switzerland.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Khammash
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D056915:DNA Copy Number Variations; D019281:Dimerization; D008956:Models, Chemical; D010363:Pattern Recognition, Automated; D010507:Periodicity; D011336:Probability; D013269:Stochastic Processes