SBML Software Summary

This page lists software known to us to provide some degree of support for reading, writing, or otherwise working with SBML. For an at-a-glance matrix summarizing key features of these software packages, please see our SBML Software Matrix page. Please use the survey form to notify us about additions and suggestions.

Simulators: Discrete stochastic

Note that several of the ODE/DAE-based simulators also include some form of stochastic simulation capability, and vice-versa.

• BetaWB - BetaWB is a collection of tools based on the programming language BlenX, explicitly designed to represent biological entities and their interactions. The BetaWB includes the BetaWB simulator, a stochastic simulator based on an efficient variant of the Gillespie Stochastic Simulation Algorithm (SSA), the BetaWB designer, a graphical editor for developing models and the BetaWB plotter, a tool to analyse the results of a stochastic simulation run.
• BioNetGen -BioNetGen is software for the specification and simulation of rule-based models of biochemical systems. In rule-based models, molecules and molecular complexes are represented using graphs, and molecular interactions and their consequences are represented using graph-rewriting rules.
• BioRica - BioRica is a high-level hierarchical modeling framework integrating discrete and continuous multi-scale dynamics. The co-existence of continuous and discrete dynamics is assured by flux connections with the continuous parts of the model. Once connected, these parts of the model act as components that can be queried for the function value, but also modified, therefore accounting for any trajectory modification induced by discrete parts of the model. BioRica is available upon request.
• Cain - Cain is an application that performs stochastic and deterministic simulations of chemical reactions. It stores models, simulation parameters, and simulation results in an XML format. The models and simulation parameters can be read from input files or edited within the program. Cain offers a variety of solvers including: Gillespie's direct method, Gillespie's first reaction method, Gibson and Bruck's next reaction method, tau-leaping, hybrid direct/tau-leaping, and ODE integration.
• COPASI - ODE & Stochastic Simulator, model builder, with multiple analysis tools. SBML Import (L1/L2), Export (L2). Free Non Commercial License; Commercial License available. (Linux/Mac/Win).
• Cyto-Sim - Stochastic simulator based on automata theory (P system). Free download. JVM Based.
• Dizzy - Chemical kinetics simulator. SBML Import/Export (L1 Subset). Includes Gillespie, Gibson-Bruck and Tau Leap stochastic and ODE/RK5 deterministic methods. LGPL, open source, Free download. (Linux/Mac/Windows).
• ESS - Exact Stochastic Simulator. Part of the UTK/ORNL Bio-SPICE tool set which includes the BioSpreadsheet SBML model editor. Requires BioSpice Dashboard. Free download. Includes Source code.
• FERN - FERN is a Java framework for the efficient simulation of chemical reaction networks. It provides a broad range of efficient and accurate algorithms both for exact and approximate stochastic simulation and a simple interface for extending to new algorithms. Furthermore, it can be used in a straightforward way both as a stand-alone program and within new systems biology applications. Finally, complex scenarios requiring intervention during the simulation progress can be modeled easily with FERN.
• Gillespie2 - from the BASIS Project. Source code.
• GNA - Genetic Network Analyzer (GNA) is a computer tool for the modeling and simulation of genetic regulatory networks. The aim of GNA is to assist biologists and bioinformaticians in constructing a model of a genetic regulatory network using knowledge about regulatory interactions in combination with gene expression data. Genetic Network Analyzer consists of a simulator of qualitative models of genetic regulatory networks in the form of piecewise-linear differential equations. Instead of exact numerical values for the parameters, which are often not available for networks of biological interest, the user of GNA specifies inequality constraints. This information is sufficient to generate a state transition graph that describes the qualitative dynamics of the network. The simulator has been implemented in Java 1.5 and has been applied to the analysis of various regulatory systems, such as the networks controlling the initiation of sporulation in B. subtilis and the carbon starvation response in E. coli.
• GnuMcSim - GNU MCSim is a free simulation package that allows you to design your own statistical or simulation models, and to efficiently perform Bayesian inference through Markov Chain Monte Carlo simulations. Standard Monte Carlo and experimental design optimization are also available. Starting with version 5.3.0, GNU MCSim can import and simulate SBML models.
• iBioSim - iBioSim is a tool that supports learning of genetic circuit models, efficient abstraction-based analysis of these models, and the design of synthetic genetic circuits. iBioSim includes project management features and a graphical user interface that facilitates the development and maintenance of genetic circuit models as well as both experimental and simulation data records. Models in iBioSim can be created using either an SBML editor or a Genetic Circuit Model (GCM) editor. (Linux/Mac/Windows)
• MODESTO - Merged ODE and Stochastic Simulator. Source code only. Linux. (MPL 1.1)
• Moleculizer - Command line stochastic simulator. Open source. (Linux) (GPL)
• MOOSE - MOOSE is the Multiscale Object-Oriented Simulation Environment. It is the base and numerical core for large, detailed simulations including Computational Neuroscience and Systems Biology. MOOSE spans the range from single molecules to subcellular networks, from single cells to neuronal networks, and to still larger systems. it is backwards-compatible with GENESIS, and forward compatible with Python and XML-based model definition standards like SBML and MorphML. MOOSE is coordinating with the GENESIS-3 project towards the goals of developing educational resources for modeling. MOOSE is open source software, licensed under the LGPL (Lesser GNU Public License). It has absolutely no warranty.
• PNK - Petri Net Simulator (JRE/SBW required) (GPL).
• SmartCell - Stochastic Simulator (Linux/Mac/Win) (Acad/NP).
• StochKit - C++ library that provides various SSA, tau-leaping and adaptive step size algorithms. Source code only. (Linux) (Acad/NP).
• StochSim Stochastic simulations with some multistate species. Open Source. (Linux/Mac/Win) (source plus binaries; PERL GUI) (GPL).
• STOCKS - SSA, Gibson-Bruck, and Tau-Leaping algorithms. Command line based tool. (source code, Linux/Windows) (GPL).
• SynBioSS - a suite of software tools for the modeling and simulation of synthetic gene constructs. SynBioSS utilizes the registry of standard biological parts, a database of kinetic parameters, and both graphical and command-line interfaces to multiscale (stochastic-discrete, stochastic-continuous and continuous-deterministic simulation) algorithms. A user can enter a sequence of BioBricks to synthesize a new gene network, obtain a set of biochemical reactions and model the dynamic behavior.
• Trelis - Monte Carlo Simulator.
• TinkerCell - TinkerCell is a visual application for constructing genetic, signaling, or metabolic networks with an extensive C and Python API. At present, the functionalities include deterministic and stochastic simulation (C libraries), steady state analysis, flux balance analysis using LPsolve C library, graph analysis through the NetworkX python module, and all the functionalities of PySCeS python module, including sensitivity and structural analysis. TinkerCell can build models by connecting modules. TinkerCell models contain meta-data for supporting a parts database. The visual display format is flexible.

Simulators: Continuous deterministic

• BIOCHAM - Programming environment with GUI, simulator, and rule-based modeling language. SBML import & export.
• BioNessie - BioNessie is a free, state-of-the-art platform-independent biochemical networks simulation and analysis software environment software. It is developed using Java technology and can run on many platforms that support JRE (Java Runtime Environment 1.5 or higher). It provides a full user-friendly Graphical User Interface (GUI) which allows the user to import, create, edit and export the biochemical models with the SBML (Systems Biology Markup Language) standard. The unique Concurrent Versions Syst ...
• BioNetGen - BioNetGen is software for the specification and simulation of rule-based models of biochemical systems. In rule-based models, molecules and molecular complexes are represented using graphs, and molecular interactions and their consequences are represented using graph-rewriting rules.
• BioRica - BioRica is a high-level hierarchical modeling framework integrating discrete and continuous multi-scale dynamics. The co-existence of continuous and discrete dynamics is assured by flux connections with the continuous parts of the model. Once connected, these parts of the model act as components that can be queried for the function value, but also modified, therefore accounting for any trajectory modification induced by discrete parts of the model. BioRica is available upon request.
• BioTapestry - Graphical model development and simulation tool for genetic regulatory networks based on JRE. Uses Java Web Start. Free download. SBML export.
• braincirc - Braincirc is an open source model development and simulation environment developed primarily for linux platforms, originally developed to simulate brain circulation (Linux).
• ByoDyn - ByoDyn includes a set of tools to 1) integrate ordinary differential equations (ODEs), including systems with events, rules (differential algebraic equations, DAE) and delays built from a given biological model; 2) stochastic simulators: SSA and tau-leap; 3) globally optimize the parameters that fit the provided experimental information and evaluate the sensitivity of the model with respect to the different parameters; 4) include the sensitivity of the parameters in an optimal experimental design pipeline based on the Fisher information matrix; and 5) Monte Carlo sampling coupled with cluster analysis and PCA to determine the global shape of the parameter landscape. The program makes use of external software, providing a Python binding schema that allows the user to easily implement new software in the desired calculation protocol.
• CellDesigner - Graphical model development and simulation tool for all types of SBML models. Includes SBGN notation. SBML import & export.
• Cell Illustrator - Graphical model editor; Petri-net based algorithm; SBML Import. Commercial. (Linux/Mac/Win).
• Cellware - Block diagram model editor & simulator. SBML import. Free download (Academic/Non-Profit) (Linux/Mac/Win).
• COPASI - ODE & Stochastic Simulator, model builder. SBML Import (L1/L2), Export (L2). Free Non Commercial License; Commercial License available. (Linux/Mac/Win).
• DBSolve - Spreadsheet editor and simulator. Free. Requires registration/email verification. License TBD ...
• E-Cell - (Linux RPM/Win). Requires Python, Numpy, GSL, Boost. Command line, scripting, and GUI. Supports ODE/DAE and Gibson-Bruck SSA models. GUI requires Gnome, gnome-python2, and pygtk. GPL with exceptions. SBML import via SBML2EML converter. Limited SBML export via ecellj converter.
• Genetdes - Network optimization using Simulated Annealing. SBML Import/Export. Free download, requires email license (CCL- AN). (Linux)
• Gepasi - Forerunner of COPASI. ODE simulations, metabolic analysis. SBML L1 Inport/Export. (Windows or Linux under Wine). Limited license.
• iBioSim iBioSim is a tool that supports learning of genetic circuit models, efficient abstraction-based analysis of these models, and the design of synthetic genetic circuits. iBioSim includes project management features and a graphical user interface that facilitates the development and maintenance of genetic circuit models as well as both experimental and simulation data records. Models in iBioSim can be created using either an SBML editor or a Genetic Circuit Model (GCM) editor. (Linux/Mac/Windows)
• Jarnac - SBW tool for metabolic analysis, includes dynamic simulation. Simulation engine for JDesigner. BSD License.
• JSim - JSim is a Java-based simulation system for building quantitative numeric models and analyzing them with respect to experimental reference data. JSim's primary focus is in physiology and biomedicine, however its computational engine is quite general and applicable to a wide range of scientific domains. JSim models may intermix ODEs, PDEs, implicit equations, integrals, summations, discrete events and procedural code as appropriate. JSim's model compiler can automatically insert conversion factors for compatible physical units as well as detect and reject unit unbalanced equations. JSim also imports the SBML and CellML model archival formats.
• Kinsolver - browser based simulation tool. Must install a java front end and compile the C/Fortran backend. Source code available. Does not appear to be currently supported (last updated 2006).
• MOOSE - MOOSE is the Multiscale Object-Oriented Simulation Environment. It is the base and numerical core for large, detailed simulations including Computational Neuroscience and Systems Biology. MOOSE spans the range from single molecules to subcellular networks, from single cells to neuronal networks, and to still larger systems. it is backwards-compatible with GENESIS, and forward compatible with Python and XML-based model definition standards like SBML and MorphML. MOOSE is coordinating with the GENESIS-3 project towards the goals of developing educational resources for modeling. MOOSE is open source software, licensed under the LGPL (Lesser GNU Public License). It has absolutely no warranty.
• Narrator - Graphical model design and simulation. Java-based, platform independent. Open source/free download (LGPL).
• Oscill8 - Bifurcation and Simulation. Windows Binary. (BSD).
• PathwayLab - Simulation, Visualization, MCA; Mathematica and Matlab integration; model creation. (Windows) (Commercial).
• Pathway Solver - ODE based simulation. Commercial. (formerly runSMBL)
• PET - PET is a graphical user interface (GUI) for discovering rate constants, of molecular network models, that fit experimental data. It is designed for use by theoretical biologists to build regulatory network models and compare the models to experimental results. (Linux/Win).
• PhysioLab Modeler - Whole organism modeling environment. Commercial.
• PK-Sim - Commercial physiologically-based pharmokinetic simulation and modeling environment.
• roadRunner - roadRunner is a high performance cellular network simulation. roadRunner accepts standard SBML Level 2 and generates the necessary ordinary differential equations that are solved either by CVODE to generate time course data or NLEQ to compute the steady state. roadRunner supports many functions, including: 1.ODE simulation and steady state analysis; 2.Conservation analysis to ensure a non-singular Jacobian; 3.Steady state metabolic control analysis; 4.Frequency domain metabolic control analysis; 5.Simple continuation of steady states
• SBML-SAT SBML-SAT implements algorithms for simulation, steady state analysis, robustness analysis and local and global sensitivity analysis for SBML models. This software tool extends current capabilities through its execution of global sensitivity analyses using multi-parametric sensitivity analysis, partial rank correlation coefficient, SOBOL’s method, and weighted average of local sensitivity analyses in addition to its ability to handle systems with discontinuous events and intuitive graphical user interface.
• SBML-PET - Parameter Estimation tool (Linux/Win)
• SIMBA Wastewater simulation. SBML Support unspecified. Commercial(?).
• SimPheny - Simulation, visualization, model management
• SBTOOLBOX2 - Model development and simulation (ODE & Stochastic); SBML Import (L1/L2), Export (L2); parameter estimation; analysis tools; Metabolic control analysis. Requires MatLab (Linux/Win/Mac) (GPL).
• SynBioSS - a suite of software tools for the modeling and simulation of synthetic gene constructs. SynBioSS utilizes the registry of standard biological parts, a database of kinetic parameters, and both graphical and command-line interfaces to multiscale (stochastic-discrete, stochastic-continuous and continuous-deterministic simulation) algorithms. A user can enter a sequence of BioBricks to synthesize a new gene network, obtain a set of biochemical reactions and model the dynamic behavior.
• TinkerCell - TinkerCell is a visual application for constructing genetic, signaling, or metabolic networks with an extensive C and Python API. At present, the functionalities include deterministic and stochastic simulation (C libraries), steady state analysis, flux balance analysis using LPsolve C library, graph analysis through the NetworkX python module, and all the functionalities of PySCeS python module, including sensitivity and structural analysis. TinkerCell can build models by connecting modules. TinkerCell models contain meta-data for supporting a parts database. The visual display format is flexible.
• VCell - VCell is a complete model building, editing and simulation environment. Includes spatial modeling capabilites, deterministic, stochastic, and hybrid algorithms. Parameter sensitivity analysis and parameter optimization. Desktop application and web-based environment. Bio- and math-based interfaces. Database and model sharing/publishing. Free, registration required. Open source, source code available upon request. (Linux/Mac/Win/Web)
• WebCell - Online simulator, model builder, metabolic controal analysis. Includes database of bimodels and JWS models. Registration required.
• xCellerator - Mathematica based ODE simulator. SBML inport/export uses MathSBML. Requires Mathematica. Free download (LGPL). (Linux/Mac/Win).
• Xholon - Model development environment, tool set, simulation. (Linux/Win) Open Source (LGPL).
• XPPAUT - ODE solver, analysis tool. Open Source. Free download. (Linux/Mac/Win)

Simulators: Spatial

• MesoRD - Reaction/Diffusion simulator. Stochastic and Deterministic simulations. Free download (GPL). (Linux/Mac/Win)
• SmartCell - Stochastic Reaction/Diffusion Simulator (Linux/Mac/Win) (Acad/NP).
• VCell -VCell is a complete model building, editing and simulation environment. Includes spatial modeling capabilites, deterministic, stochastic, and hybrid algorithms. Parameter sensitivity analysis and parameter optimization. Desktop application and web-based environment. Bio- and math-based interfaces. Database and model sharing/publishing. Free, registration required. Open source, source code available upon request. (Linux/Mac/Win/Web).

Simulation and Programming Environments

• acslextreme is a commercial modeling environment that uses a script language called CSL. Has SBML import. Windows only.

• For Mathematica
  • MathSBML - SBML import/export and simulation within Mathematica.
  • PathwayLab - Stand alone simulation; Visualization; MCA; Mathematica and Matlab integration; model creation. (Windows) (Commercial).
  • xCellerator - requires MathSBML for SBML input/export.
• For MATLAB
  • SBTOOLBOX² from Henning Schmidt. Requires SBML Toolbox.
  • SBMLToolbox from the SBML Team.
  • SimBiology from The MathWorks includes both stochastic and deterministic simulation suport and a GUI model builder.
  • BioSens - ODE Simulation & Sensitivity analysis for BioSpice Dashboard Dashboard. Requires dashboard, Matlab, XPP, Cygwin, libSBML, DASPK, Tapenade. Requires Biospice dashboard, Matlab, XPP, Cygwin, libSBML, DASPK, Tapenade. Free download (License unspecified). (Windows)
  • BSTLAB - GMA and S-Systems based toolbox for Biochemical Systems Theory.
  • CellNetAnalyzer (formerly FluxAnalyzer) - CellNetAnalyzer (CNA) is a MATLAB toolbox providing a comprehensive and user-friendly environment for structural analysis of biochemical networks. CNA supports mass-flow (metabolic, stoichiometric) and signal-flow (signaling, regulatory) networks and provides various algorithms for functional network analysis such as FBA, flux analysis, elementary modes (mass-flow netw.) or signaling paths, feedback loops, global interdependencies, logical I/O analysis, intervention sets (signal-flow netw.).
  • COBRA Toolbox - The COnstraint-Based Reconstruction and Analysis Toolbox for Matlab includes implementations of many of the commonly used forms of constraint-based analysis such as FBA, gene deletions, flux variability analysis, sampling, and batch simulations together with tools to read in and manipulate constraint-based models.
  • DOTcvpSB - MatLab toolbox for optimization of models.
  • Metatool - A tool for metabolic pathway analysis with the main focus in elementary modes calculation. Enzyme subsets and conservation relations are also determined.
  • PathwayLab - Stand alone simulation; Visualization; MCA; Mathematica and Matlab integration; model creation. (Windows) (Commercial).
  • PottersWheel - ODE based Simulation, model fitting, visualization, clustering, model design. (Free download; Optimization toolbox recommended).
  • RMBNToolbox - Toolbox for generating random notebooks (GPL).
• For Octave (Some MATLAB tools may also work in Octave)
  • Simpathica - ODE based simulation. Part of BioSpice.
• For Python and SciPy
  • ByoDyn - ODE/DAE/delays; parameter optimization; sensitivity analysis. Terminal based. Free Download vis SF (GPL, includes source). Requires Python, SciPy, f2py, libSBML 2.3.4++, PORT, Gnuplot. Optional Octave (required for DAE's), Open Modelica (required for DAEs with events), Open MPI, Scientific Python. SBML import. (Linux/Mac)
  • ModelMaGe - generates SBML or Copasi candidate models by removing specified model components from a given master model. modelMaGe automatically documents candidate models, automatically fits candidate models to data using CopasiSE, and finally provides a ranking of candidate models fits based on the AIC.
  • Netbuilder' - Tool for specification and simulation of models of well-stirred (bio)chemical reaction systems, with options facilitating modelling of complex control interactions. Petri-net (to user) and matrix (to simulation engine) model representation. Supports DAE, stochastic, deterministic, and full hybrid simulation.
  • pysbml for Python - library for interfacing with SBML in Python. Uses SciPy.
  • PySCeS requires SciPy; includes ODE solve, MCA, bifurcation tools, parametric scanning. SBML import/export. Open source (GPL).
  • semanticSBML - Package that facilitates model merging (GPL).
  • SloppyCell - Simulation Package (ODE and SSA). Uses NumPy, SciPy, matplotlib. Open Source
  • Tide - Tide is a tool for the automatic identification of optimal drug targets in kinetic models based on ordinary differential equations. Give a model in the popular SBML format it will identify promising drug targets for different effective modifier concentration
  • TinkerCell - See description above under simulators.
• For R
  • RSBML - SBML interface library for R (GPL). (available from CRAN).
  • SBMLR - SBML interface library for R.
  • RANGE - Random network generator. Noise added by R-script. Source code in C, yacc, lex. (GPL).

Flux / Metabolic Analysis

• BioMet Toolbox The BioMet ToolBox, is a web-based resource for analysis of high-throughput data, together with methods for flux analysis (fluxomics) and integration of transcriptome data exploiting the capabilites of metabolic networks described in genome scale models.
• CellNetAnalyzer (formerly FluxAnalyzer) - CellNetAnalyzer (CNA) is a MATLAB toolbox providing a comprehensive and user-friendly environment for structural analysis of biochemical networks. CNA supports mass-flow (metabolic, stoichiometric) and signal-flow (signaling, regulatory) networks and provides various algorithms for functional network analysis such as FBA, flux analysis, elementary modes (mass-flow netw.) or signaling paths, feedback loops, global interdependencies, logical I/O analysis, intervention sets (signal-flow netw.).
• COBRA Toolbox - The COnstraint-Based Reconstruction and Analysis Toolbox for Matlab includes implementations of many of the commonly used forms of constraint-based analysis such as FBA, gene deletions, flux variability analysis, sampling, and batch simulations together with tools to read in and manipulate constraint-based models.
• COPASI - includes MCA (see listing under simulators).
• Fluxor - Flux analysis. Free, part of BioSpice tool set. Linux.
• Jarnac - SBW tool for metabolic analysis. Based on SCAMP. Includes dynamic simulation. BSD License.
• MetaFluxNet - Model creator, manager, flux and metabolic pathway analysis and visualization. Free academic version with limited functionality. Windows only (req. .NET). User must send hard-copy of signed license by mail before s/w can be downloaded.
• Pathway Analyser - Flux analysis. Free download, open source (Linux).
• MMT2 - Metabolic modeling, model fitting, automated high-performance code generation. (Linux only).
• SBTOOLBOX2 - MCA: Steady state control coefficients and elasticities; Structural analaysis: conservation relation analysis; model development; simulation; SBML Import/Export; parameter estimation; analysis tools. Requires MatLab (Linux/Win/Mac).
• TinkerCell - See description above under simulators.
• WebCell - Online MCA, Visualization, and dynamic simulation.
• WinSCAMP - Windows Binary for SCAMP. Metabolic analysis, ODE solver. Binary download only. Source code on request.

Modeling Frameworks for Biology

• Bio-Spice - Large collection of tools, integrated via a "Dashboard." Free download (BSD), various platforms.
• SBW - Systems Biology Workbench. A framework for connecting and running various applications written in different languages or on different systems, and a collection of available modules for model development, analysis, and simulation. Free/Open Source. (BSD)
• Teranode - Suite of tools for model management, design, and simulation. (Linux/Mac/Windows) Commercial (30-day trial available).

SBML and Modeling libraries

• libSBML for C, C++, Java, Lisp, Python, Perl, Matlab, Octave, and Ruby. Free Download (LGPL). (Linux/Mac/Win).
• cl-sbml Common Lisp library for SBML. Uses libSBML. License unspecified. Source Code (Lisp). Free Download via CVS.
• SBML ODE Solver - C-based simulation library and API for SBML. Uses Sundials. Source Code (Linux/Max/Win) (LGPL).

Model Management, Data Integration, and Analysis

• BioPathwise - BioPathwise is a pathway-centric environment for interdisciplinary collaborative research. The main interface is a pathway whiteboard that allows graphic representation of pathways, visualization of experimental data, pathway simulation, statistical analysis and regression. Extensible via an open API.
• Medicel - commercial data integration framework.
• MetExplore - A web server to link metabolic experiments and genome-scale metabolic networks. MetExplore contains network original filters, allows to export in SBML and visualise filtered metabolic networks, and map masses from metabolic experiments onto complete metabolic networks.
• Pathway Tools extracts and integrates information from pathway/genome databases (see [http:biocyc.org/ BioCyc]); metabolic analysis; gene code prediction; operon prediction; gene expression analysis. Optional support: Oracle or MySQL, Browser, BLAST, Marvin Msketch, JME/OpenBabel. SBML support via BioCyc. Free academic; fee for commercial. License application must be reviewed by SRIC before download. SRI unique license. (Linux/Windows/Solaris/Mac).
• PATIKA - Pathway database integration; pathway visualization and analysis. Online tool only. (Acad/NP)
• ProcessDB - Model design and management. Commercial.
• PROTON - Integrated modeling environment. Reconstructs biochemical systems from molecular databases in an automated and user-centric way. Fuses information from distributed databases and the reconstruction of systems is interactively controlled by the user. The approach is based on different layers which allow the integrative modelling of biochemical systems at multiple levels. ODE based modeling and simulation. (Free Download. Optional Server, Windows; Client: Linus/Windows/Mac).
• ReMatch - ReMatch is a web-based tool for integration of user-given stoichiometric metabolic models into a database collected from public data sources such as KEGG, MetaCyc, CheBI and ARM. ReMatch is geared particularly towards 13C metabolic flux analysis: it is possible to augment the model with carbon mappings and export the model to analysis in 13C flux analysis software
• SCIPath - microarray data management. (Linux/Windows).
• SIGNALIGN - online pathway alignment service.
• SigPath Bioinformatic database and pathway management (GPL).
• SRS - Data integration for bioinformatics. Commercial.

Model Development Tools

• ALC - ALC (Automated Layer Construction) (Koschorreck et al., BMC Systems Biology 2008, 2:91) is a computer program that highly simplifies the building of reduced modular models, according to the layer-based approach. The model is defined using a simple but powerful rule-based syntax that supports the concepts of modularity and macrostates. ALC performs consistency checks on the model definition and provides the model output in different formats (C MEX, MATLAB, Mathematica and SBML) as ready-to-run simulation files. ALC also provides additional documentation files that simplify the publication or presentation of the models. The tool can be used offline (which requires Perl) or via a form on the ALC website. ALC can be downloaded from the ALC website or from SourceForge.
• Antimony - libAntimony is a C/C++ library that can parse Antimony-formatted models, convert them to SBML, and provides an API to allow other tools access to model elements. Antimony models are modular, text-based, human readable and writable, largely compatible with SBML, and have a special syntax for creating genetic networks.
• Asmparts - Produces models of biological systems by assembling models from biological parts.
• BALSA - Front end for Sigtran (inactive?)
• BioCharon includes a suite of tools for developing models for use with CHARON. It includes the graphical BioSketchPad for desigining models, a hybrid SBML/C++ language model builder, and a metabolic analyzer.
• BiologicalNetworks pathway model development supports SBML Import/Export (only supports simple mass action kinetics); visualization; data management; network/metabolic analysis; clustering. No simulation engine. Free academic download (Java web start, Windows/Linux/Mac).
• BioNetGen - BioNetGen is a software system for the specification and simulation of rule-based models of biochemical systems. In rule-based models, molecules and molecular complexes are represented using graphs, and molecular interactions and their consequences are represented using graph-rewriting rules. Open source. Download requires email based registration. Requires Perl. Optional GUI uses JRE. (Linux/Mac/Win)
• Bio Sketch Pad - graphical model design tool, front end for BioCharon
• BioSpreadsheet - SBML model editor. Part of the UTK/ORNL Bio-SPICE tool set which includes the Exact Stochastic Simulator (ESS). Requires BioSpice Dashboard. Free download. Includes Source code.
• BioTapestry - Graphical model development and simulation tool for genetic regulatory networks based on JRE. Uses Java Web Start. Free download. SBML export.
• CADLIVE - Graphical Model Design Tool. Includes an ODE simulator. SBML L2 Import/Export. Windows Only. Free Download.
• Cell Illustrator - Graphical model editor; Petri-net based simulation algorithm; SBML Import. Commercial. (Linux/Mac/Win).
• COPASI - includes an SBML model builder (see listing under simulators).
• Cystoscape - Graphical model design and layout. SBML L2 Import. Free download (LGPL) (Linux/Mac/Win).
• Edinburgh Pathway Editor (EPE) - Edinburgh Pathway Editor is a biological pathway drawing/editing application. Currently it can draw diagrams using SBGN PD Level 1, Cytoscape and Metabolic notations. It can export SBML Level 2 v3 and BioPAX Level 3 from the metabolic notation and BioPAX export for SBGN will be coming soon. It is completely customisable and can be configured to support a wide variety of graphical notations. In addition it has an extensible architecture that allows addition exporters to be added. The ability to import SBML models will come soon.
• HSMB - Hybrid SBML Model Builder for BioCharon.
• JDesigner - Graphical model design tool. Typically uses Jarnac as a simulation engine via SBW. Free/Open Source (LGPL).
• JigCell - Model development tool and run manager. Depends on XPP/XPPAUT, JRE. Part of Bio-Spice Tool Kit. Free Download (Biospice/DARPA license) (Linux/Mac/Windows). Inlcudes SBML L2 Parser. Not updated since 2004. Some pages are dead.
• Karyote - Online model development tool based on online database of parts. Claims to have some sort of simulator and SBML support. Level unclear. Documentation absent.
• MONOD "Modeler's Notebook and Data Store" model annotation manager. (Linux/Mac OS) Open Source, Must build from source (LGPL).
• Pathway Builder - Graphical model design. Part of Bio-Spice. (BioSpice BSD License)
• PathwayLab - Deterministic simulation; Visualization; MCA; Mathematica and Matlab integration; model creation. (Windows) (Commercial).
• PAYAO - PAYAO is a community collaborative web service platform for gene-regulatory and biochemical pathway model curation.
• ProMoT - ProMoT (for Process Modeling Tool) is software for the set-up and manipulation of models of complex technical or biological systems. Key features are the support of modular models, specialized libraries for different application areas and advanced graphical support. Dynamic models can contain DAE and discrete events for simulation in DIVA, Diana or Matlab. Logical/boolean models are exported to CellNetAnalyzer. (Linux).
• SBMLeditor - SBML Model editor. Free download (GPL). (Linux/Mac/Win).
• SBML Shorthand - python tools for converting SBML Shorthand to/from SBML
• Sycamore - Model design, integration with SABIO-RK, integration with simulation, and parameter estimation.

Model Visualization Tools

Please note that most of the model simulation, development, and analysis tools listed elsewhere on this page include some form of visualization.

• COPASI - shows the time course simulation results overlaid on a graphical network layout of the model (see listing under simulators).
• PaVESy - Pathway Visualization Editing System. Java based. (Linux/Mac/Win). Free download.
• SBML Layout Viewer will automatically generate an SBML Layout and render the image from an SBML file. Web based.
• SimWiz Visualizes simulation outputs from tools such as Copasi and STODE. (Linux/Win) (European Media License)
• VANTED - "Visualization and Analysis of Networks containing Experimental Data" - analysis and visualization of graph heirarchies. Requires JRE. Java web start. Includes all other dependencies. Various free licenses for dependencies.

Model Repositories, Test Suites, and Databases

• Stochastic Test Suite from BASIS
• BiGG Database of human, yeast and bacterial metabolites, pathways and reactions as well as SBML reconstructions for metabolic modeling.
• Biomodels Database is a curated database of published quantitative models that may be downloaded in SBML. Some models are also available in CellML, SciLab, XPP, and BioPAX format and most can be simulated via JWS Online.
• BioCyc - collection of pathway/genome databases. May be downloaded in SBML, BioPAX, or flat format. Free limited academic license (detailed). May be explored with Pathway Tools
• CycSim CycSim is a web application dedicated to in silico experiments with genome-scale metabolic models coupled to the exploration of knowledge from BioCyc and KEGG. it supports the design of knockout experiments: simulation of growth phenotypes of single or multiple gene deletions mutants on specified media, comparison of these predictions with experimental phenotypes and direct visualization of both on metabolic maps. CycSim also functions as an online repository of genome-scale metabolic models.
• JWS Online - Online database and simulator.
• kineticon - online resource for kinetic data, reactions, enzymes, pathways. SBML L2V1 Export.
• Meta-All - Pathway database manager.
• NetPro - Molecular interaction database (commercial).
• PathArt - Pathway database collection. (Commercial)
• Panther Pathway - Pathway database (online resource).
• Reactome - Pathway database (online resource).
• SABIO-RK - Reaction and Kinetic data base (online resource). See also Sycamore.
• SIGMOID - Model database, explorer, visualization, Cellerator-based simulations as a web service.

SBML Conversion Tools

Many of other tools listed on this page include translators between SBML and their tool-unique language; this list is for tools that only do translation, independent of a specific tool.

• CellML2SBML - Converts CELLML to SBML
• Antimony2SBML/sbml2Antimony - Antimony2sbml and sbml2antimony convert models between the SBML and Antimony formats. See separate listing above for Antimony.
• COPASI - includes conversion from SBML to XPPAut, Berkeley Madonna, C source code; and import from Gepasi. See more under simulators.
• ecellj - converts between ecell models and various other formats including SBML and open office spreadsheets.
• KeggConverter - Conversion of KGML to SBML
• KEGG2SBML - Converts KEGG models to SBML

SBML Extensions

• CLEML Carbon Labeling Experiment Markup Language. The libCLEML is freely downloadable (GPL). (Linux/Win).

Analysis and Utility Programs

• BiNoM - Biological Network Manager. Network design and manipulation. Visualization. Model conversion (CellDesigner, BioPAX); Structural Analysis; BioPAX Queries. Available as an independent library or Cytoscape plugin.
• CellMC - CellMC is a program generator that emits highly optimized executables realizing the stochastic simulation algorithm (SSA) given a model expressed as SBML (Level 2). It works on Intel/AMD based PCs and Cell/BE platforms (e.g. Sony PS3, IBM QS22).
• COPASI - includes export of system to MathML and latex as well as various other formats (see listing under conversion tools; simulators).
• DOTcvpSB - MatLab toolbox for optimization of models.
• GRENDEL - GRENDEL (Gene Regulatory Network Decoding Evaluations tooL), generates random gene regulatory networks according to user specified constraints on the network topology and kinetics (in addition to generating random topologies, it can also take a predefined topology as input). It then outputs SBML to define the state of each regulatory network under various user specified experimental designs, which can be integrated to produce simulated gene expression data.
• Jacobian Viewer - The Jacobian matrix is of central importance in the analysis of a computational model. The Jacobian specifies the local dynamics of the model. The entries in the matrix indicate the influence of model variables on the rates of change.The Jacobian Viewer will dynamically show these changes. In order to do so we generate a dependency graph for a computational model, with nodes denoting all species in the model and arcs denoting the influence of one species on the rates of change of another species. This provides insight of how those changes occur. The researcher is of course able to change the time-steps taken by the simulator as well as the starting point of the simulation.
• SAINT - The creation of accurate quantitative Systems Biology Markup Language (SBML) models is a time-intensive manual process. Modelers need to know and understand both the systems they are modeling and the intricacies of SBML. However, the amount of relevant data for even a relatively small and well-scoped model is overwhelming. Saint, an automated SBML annotation integration environment, aims to aid the modeler and reduce development time by providing extra information about any given SBML model in an easy-to-use interface. Saint accepts SBML-formatted files and integrates information from multiple databases automatically. Any new information that the user agrees with is then automatically added to the SBML model. The purpose of Saint is to aid the researcher in the difficult task of information discovery by seamlessly querying multiple databases and providing the results of that query within the SBML model itself. By providing a modeling interface to existing data integration resources, modelers are able to add information to models quickly and simply.
• SBMLsqueezer - Plug-in for CellDesigner 4.0 that generates rate equations for biochemical networks according to SBGN and the context of the reaction. Rate laws include generalized mass action; detailed enzyme kinetics (Michaelis-Menten) for up to two substrates or products; Hill equations; or the approximative convenience rate law. User defined settings specify which equation to apply for any type of reaction. Equations can be created using contextual menus. MathML is inserted directly into the SBML file. LaTeX or Text ODE Export.
• SBML-SAT SBML-SAT implements algorithms for simulation, steady state analysis, robustness analysis and local and global sensitivity analysis for SBML models. This software tool extends current capabilities through its execution of global sensitivity analyses using multi-parametric sensitivity analysis, partial rank correlation coefficient, SOBOL’s method, and weighted average of local sensitivity analyses in addition to its ability to handle systems with discontinuous events and intuitive graphical user interface.
• Tide - Tide is a tool for the automatic identification of optimal drug targets in kinetic models based on ordinary differential equations. Give a model in the popular SBML format it will identify promising drug targets for different effective modifier concentrations.

Authors

Bruce E. Shapiro and Mike Hucka.