Multi-algorithm, multi-timescale cell simulation using E-Cell3
Kouichi Takahashi1, Kazunari Kaizu2, Bin Hu, Yohei Yamada, Masaru Tomita
1shafi@sfc.keio.ac.jp, Institute for Advanced Biosciences, Keio University; 2t00220kk@sfc.keio.ac.jp, 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 http://www.e-cell.org.