Multiscale Stochastic Simulation of Reaction-Transport Processes Applications in Molecular Systems Biology

Abstract: Quantitative descriptions of reaction kinetics formulated at the stochastic mesoscopic level are frequently used to study various aspects of regulation and control in models of cellular control systems. For this type of systems, numerical simulation offers a variety of challenges caused by the high dimensionality of the problem and the multiscale properties often displayed by the biochemical model.In this thesis I have studied several aspects of stochastic simulation of both well-stirred and spatially heterogenous systems. In the well-stirred case, a hybrid method is proposed that reduces the dimension and stiffness of a model. We also demonstrate how both a high performance implementation and a variance reduction technique based on quasi-Monte Carlo can reduce the computational cost to estimate the probability density of the system.In the spatially dependent case, the use of unstructured, tetrahedral meshes to sample realizations of the stochastic process is proposed. Using such meshes, we then extend the reaction-diffusion framework to incorporate active transport of cellular cargo in a seamless manner. Finally, two multilevel methods for spatial stochastic simulation are considered. One of them is a space-time adaptive method combining exact stochastic, approximate stochastic and macroscopic modeling levels to reduce the simualation cost. The other method blends together mesoscale and microscale simulation methods to locally increase modeling resolution.