Multi-algorithm, multi-timescale cell simulation using E-Cell3

Kouichi Takahashi1, Kazunari Kaizu2, Bin Hu, Yohei Yamada, Masaru Tomita, Institute for Advanced Biosciences, Keio University;, Institute for Advanced Biosciences, Keio University

An object-oriented 'meta-algorithm' capable of composite simulation of many components driven by different algorithms and different timescales is developed. This algorithm also allows discrete and continuous simulation components to coexist. A discrete-event scheduler for efficient scheduling of simulation components, and Hermite polynomial interpolation for continuous-continuous and continuous-discrete interactions between the components are used. Several plug-in 'algorithm-modules' including Gillespie-Gibson, Dormand-Prince 5(4)7M, Fehlberg 2(3), discrete-time simulator (for difference equations and discrete-time cellular automata), ESSYNS method for S-System and GMA canonical forms of differential equations, and an algebraic equation module are implemented. An E. coli heat-shock model that combines the discrete-event Gillespie-Gibson stochastic algorithm and a deterministic differential equation solver, and a multi-timescale model with multiple ordinary differential components have been constructed. These demonstration models showed dramatic performance improvements against conventional synchronous, single-scheme simulations without significant compromise in accuracy. The importance of computer simulation in understanding cellular processes is now widely accepted, and a variety of simulation algorithms useful for studying certain sub-systems have been designed. Many of these are already widely used, and a large number of models constructed on these existing formalisms are available. This method provides a solution to a significant computational challenge, that is, how we can integrate such sub-cellular models running on different types of algorithms to construct higher order models. An implementation of the method is available as part of E-Cell 3 software downloadable from