Proceedings of the 38th conference on Winter simulation
Challenges for modeling and simulation methods in systems biology
Proceedings of the 38th conference on Winter simulation
Nested stochastic simulation algorithms for chemical kinetic systems with multiple time scales
Journal of Computational Physics
A parallel and distributed discrete event approach for spatial cell-biological simulations
ACM SIGMETRICS Performance Evaluation Review
FMSB '08 Proceedings of the 1st international workshop on Formal Methods in Systems Biology
An Exact Brownian Dynamics Method for Cell Simulation
CMSB '08 Proceedings of the 6th International Conference on Computational Methods in Systems Biology
Large-Scale Design Space Exploration of SSA
CMSB '08 Proceedings of the 6th International Conference on Computational Methods in Systems Biology
Multi-resolution spatial simulation for molecular crowding
Proceedings of the 40th Conference on Winter Simulation
Research Article: Hybrid stochastic simulations of intracellular reaction-diffusion systems
Computational Biology and Chemistry
Regenerative systems: challenges and opportunities for modeling, simulation, and visualization
Proceedings of the Fourth International ICST Conference on Performance Evaluation Methodologies and Tools
Algorithmic algebraic model checking IV: characterization of metabolic networks
AB'07 Proceedings of the 2nd international conference on Algebraic biology
Hierarchical modeling for computational biology
SFM'08 Proceedings of the Formal methods for the design of computer, communication, and software systems 8th international conference on Formal methods for computational systems biology
Discrete event multi-level models for systems biology
Transactions on Computational Systems Biology I
A specification language and a framework for the execution of composite models in systems biology
Transactions on Computational Systems Biology VII
Spatial modeling in cell biology at multiple levels
Proceedings of the Winter Simulation Conference
Multiscale stochastic simulations of chemical reactions with regulated scale separation
Journal of Computational Physics
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Motivation: Many important problems in cell biology require the dense nonlinear interactions between functional modules to be considered. The importance of computer simulation in understanding cellular processes is now widely accepted, and a variety of simulation algorithms useful for studying certain subsystems have been designed. Many of these are already widely used, and a large number of models constructed on these existing formalisms are available. A significant computational challenge is how we can integrate such sub-cellular models running on different types of algorithms to construct higher order models. Results: A modular, object-oriented simulation meta-algorithm based on a discrete-event scheduler and Hermite polynomial interpolation has been developed and implemented. It is shown that this new method can efficiently handle many components driven by different algorithms and different timescales. The utility of this simulation framework is demonstrated further with a 'composite' heat-shock response model that combines the Gillespie--Gibson stochastic algorithm and deterministic differential equations. Dramatic improvements in performance were obtained without significant accuracy drawbacks. A multi-timescale demonstration of coupled harmonic oscillators is also shown. Availability: An implementation of the method is available as part of E-Cell Simulation Environment Version 3 downloadable from http://www.e-cell.org/software. Benchmark models are included in the package, and also available upon request. Supplementary information: Complete lists of reactions and parameters of the heat-shock model, and more results are available at http://www.e-cell.org/bioinfo/takahashi03-1-supp.pdf