title: A hybrid multiscale Monte Carlo algorithm (HyMSMC) to cope with disparity in time scales and species populations in intracellular networks.
abstract: BACKGROUND
  The fundamental role that intrinsic stochasticity plays in cellular functions has been shown via numerous computational and experimental studies. In the face of such evidence, it is important that intracellular networks are simulated with stochastic algorithms that can capture molecular fluctuations. However, separation of time scales and disparity in species population, two common features of intracellular networks, make stochastic simulation of such networks computationally prohibitive. While recent work has addressed each of these challenges separately, a generic algorithm that can simultaneously tackle disparity in time scales and population scales in stochastic systems is currently lacking. In this paper, we propose the hybrid, multiscale Monte Carlo (HyMSMC) method that fills in this void.
  
  
  RESULTS
  The proposed HyMSMC method blends stochastic singular perturbation concepts, to deal with potential stiffness, with a hybrid of exact and coarse-grained stochastic algorithms, to cope with separation in population sizes. In addition, we introduce the computational singular perturbation (CSP) method as a means of systematically partitioning fast and slow networks and computing relaxation times for convergence. We also propose a new criteria of convergence of fast networks to stochastic low-dimensional manifolds, which further accelerates the algorithm.
  
  
  CONCLUSIONS
  We use several prototype and biological examples, including a gene expression model displaying bistability, to demonstrate the efficiency, accuracy and applicability of the HyMSMC method. Bistable models serve as stringent tests for the success of multiscale MC methods and illustrate limitations of some literature methods.
authors.affiliation: Department of Chemical Engineering, University of Delaware, Newark, Delaware 19716, USA. samant@udel.edu <samant@udel.edu>
authors.forename: Asawari
authors.initials: A
authors.lastname: Samant
authors.forename: Babatunde A
authors.initials: BA
authors.lastname: Ogunnaike
authors.forename: Dionisios G
authors.initials: DG
authors.lastname: Vlachos
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D008954:Models, Biological; D015233:Models, Statistical; D009010:Monte Carlo Method; D020543:Proteome / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology*; D013269:Stochastic Processes; D013997:Time Factors
chemical_list: D020543:Proteome