The systems biology simulation core algorithm

Abstract

BackgroundWith the increasing availability of high dimensional time course data for metabolites, genes, and fluxes, the mathematical description of dynamical systems has become an essential aspect of research in systems biology. Models are often encoded in formats such as SBML, whose structure is very complex and difficult to evaluate due to many special cases.ResultsThis article describes an efficient algorithm to solve SBML models that are interpreted in terms of ordinary differential equations. We begin our consideration with a formal representation of the mathematical form of the models and explain all parts of the algorithm in detail, including several preprocessing steps. We provide a flexible reference implementation as part of the Systems Biology Simulation Core Library, a community-driven project providing a large collection of numerical solvers and a sophisticated interface hierarchy for the definition of custom differential equation systems. To demonstrate the capabilities of the new algorithm, it has been tested with the entire SBML Test Suite and all models of BioModels Database.ConclusionsThe formal description of the mathematics behind the SBML format facilitates the implementation of the algorithm within specifically tailored programs. The reference implementation can be used as a simulation backend for Java™-based programs. Source code, binaries, and documentation can be freely obtained under the terms of the LGPL version 3 from http://simulation-core.sourceforge.net. Feature requests, bug reports, contributions, or any further discussion can be directed to the mailing list simulation-core-development@lists.sourceforge.net.

SBMLSimulator: A Java Tool for Model Simulation and Parameter Estimation in Systems Biology

“…The simulation of a model is done with the SBSCL [5] and JSBML [27] is used as internal data structure for model representation. The SBSCL outputs the simulation results in a specific format, which enables SBMLsimulator to plot the time course of the model's species.…”

“…Biological network models are typically encoded in Extensible Markup Language (XML)-based description formats [2], such as the Systems Biology Markup Language (SBML) [3]. In the most common scenario, such a model can be interpreted in terms of an ordinary differential equation (ODE) system with additional constructs, such as discrete events, delays, or algebraic rules [4,5]. A graphical display of the resulting curves can greatly facilitate the analysis of the system.…”

“…With little effort, SBMLsimulator can then be modified to take advantage on all enhancements. The SBSCL already supports all elements of SBML and comprises several ODE solvers including a solver for stiff ODE systems (for a comparison of SBSCL to related simulation frameworks see [5] and the up-to-date comparisons of the SBML standard compliance [22]). EvA2 provides a plethora of nature-inspired heuristic optimization algorithms, such as evolution strategies [23], genetic algorithm [24], differential evolution [25], and particle swarm optimization [26], and many more.…”

phraSED-ML: A paraphrased, human-readable adaptation of SED-ML

“…6 Other simulators include the SBW Simulation Tool 7 and the Systems Biology Simulation Core Library. 8 Apart from generic XML editors, some others let you edit or create SED-ML. SED-ML Script 9 defines a script-based language that is closely tied to SED-ML itself: each script function adds a particular SED-ML element to a document, with the arguments of that function setting all of the particular attributes and child elements of that root element.…”

libRoadRunner: A High Performance SBML Compliant Simulator

“…To resolve this issue various groups have built simulators as reusable libraries. Most notable of these are COPASI [2], libSBMLSim [9], RoadRunner C# [7], SOSLib [5] and SBSCL [3]. Despite all these efforts, finding a simulator that is easy-to-use, has good SBML-compliance, is capable of handling complex models and fast enough to run thousands of models is challenging; for example, in multi-cell simulators such as CompuCell3D.…”