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.

Note that several of the ODE/DAE-based simulators also include some form of stochastic simulation capability, and vice-versa. Also most of the model simulation, development, and analysis tools listed elsewhere on this page include some form of visualization.

• ABC-SysBio — ABC-SysBio implements likelihood free parameter inference and model selection in dynamical systems. It is designed to work with both stochastic and deterministic models written in Systems Biology Markup Language (SBML). ABC-SysBio is a Python package that combines three algorithms: ABC rejection sampler, ABC SMC for parameter inference and ABC SMC for model selection.
• AMIGO — AMIGO means Advanced Model Identification using Global Optimization. AMIGO is a multi-platform (Windows and Linux) matlab-bsed toolbox which covers all the steps of system identification in systems biology. This includes: local and global sensitivity analysis, local and global ranking of parameters, parameter estimation, identifiability analysis and optimal experimental design.
• APMonitor — The APMonitor Modeling Language is optimization software for differential and algebraic equations. It is coupled with large-scale nonlinear programming solvers for data reconciliation, real-time optimization, dynamic simulation, and nonlinear predictive control. It is available as a free web service through MATLAB or Python.
• AutoSBW — A frontend around AUTO to simplify bifurcation analysis. The program allows to open SBML models (up to Level 3), and interprets them using AUTO 2000.
• Bifurcation Discovery Tool — The Bifurcation Discovery Tool uses a genetic algorithm to search for Hopf bifurcations, turning points, and bistable switches. The user can select parameters to be searched, admissible parameter ranges, and the nature of the bifurcation to be sought. The tool returns parameter values for the model for which the particular behavior is observed.
• BioBayes — software package for applying the Bayesian inferential methodology to problems in systems biology.
• 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.
• BioPARKIN — Robust and reliable parameter identification (e.g. rate constants) in biology-related systems described by (sets of) ODEs or DAEs from given measurements, based on an affine covariant Gauss-Newton algorithm. Additionally, providing a sensible, parameter depending sensitivity analysis for the ODE/DAE systems.
• BoolNet — An R package for the generation, reconstruction, simulation and analysis of synchronous, asynchronous, and probabilistic Boolean networks
• 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. Furtermore, a webserver has been developed to manage the models, calculations and results easily.
• CADLIVE — CADLIVE (Computer-Aided Design of LIVing systEms) is a comprehensive computational tool for constructing large-scale biological network maps, analyzing the topological features of them, and simulating their dynamics. Using CADLIVE, we rationally design a biological system at the molecular interaction level for an engineering purpose.
• CARMEN — CARMEN provides the KGML-based model generation of metabolic pathways based on KEGG database information and the application of template-based models for comparative genomics. This software will be of interest in genome sequencing projects aiming at the rapid analysis and visualization of microbial metabolic features. The KGML-based model generation facilitates a high-speed generated overview of the metabolic repertoire. The comparative analysis of newly sequenced organisms is highly desirable to identify organism-specific features. The reconstructed networks are stored in standardized SBML format.
• CellNetAnalyzer — CellNetAnalyzer (CNA) is a package for MATLAB and provides a comprehensive and user-friendly environment for structural and functional analysis of biochemical networks. CNA facilitates the analysis of metabolic (stoichiometric) as well as signaling and regulatory networks solely on their network topology, i.e. independent of kinetic mechanisms and parameters. CNA provides a powerful collection of tools and algorithms for structural network analysis which can be started in a menu-controlled manner within interactive network maps. Recently, API functionalities have been added to enable interested users to call algorithms of CNA from external programs. Applications of CNA can be found in systems biology, biotechnology, metabolic engineering, pharmacology, microbiology, chemical engineering.
• COBRA — 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 — COPASI is a software application for simulation and analysis of biochemical networks and their dynamics. COPASI is a stand-alone program that supports models in the SBML standard and can simulate their behavior using ODEs or Gillespie's stochastic simulation algorithm; arbitrary discrete events can be included in such simulations. COPASI provides an C++ API with language bindings for Perl, python, R, Java, and Octave and is able to communicate with the Systems Biology Workbench COPASI carries out several analyses of the network and its dynamics and has extensive support for parameter estimation and optimization. COPASI provides means to visualize data in customizable plots, histograms and animations of network diagrams. Please see the COPASI detailed description for a complete list of features. (You can view the test results for this system in the SBML Test Suite Database.)
• CRdata — CRdata.org offers menu-driven access to the Amazon Elastic Computing Cloud (EC2) and related resources for bioinformatic computing with R and Bioconductor. Users can launch their own processing nodes, and share nodes, scripts, and data with others if they wish.
• DBSolve — DBSolveOptimum is a free software for kinetic modeling of metabolic pathways, analysis, and fitting parameters to experimental data. The program has text-based user interface for model description and graphical interface for data analysis. In addition to standart algorithms of simulation (ODE solver, explicit solver, steady-state analysis) the software include also automated local sencetivity analysis, parameters optimization procedures and bifurcaion analysis. The last version of DBSolveOptimum includes advanced tool for data visualization.
• DOTcvpSB — MatLab toolbox for optimization of models.
• Facile — Facile / EasyStoch. A command-line network compiler for systems biology. Facile reads models given in a simple and human-readable textual input format and exports the model in a format for readable by Matlab, Mathematica, Maple, XPP/AUTO. Other tools are supported via SBML export. For stochastic simulations, Facile uses the EasyStoch stochastic simulator. An important feature of EasyStoch that distinguishes it from other Gillespie-algorithm implementations is that it is capable of simulating dynamically changing or noisy biochemical parameters (i.e. extrinsic noise).
• FAME — The Flux Analysis and Modeling Environment (FAME) is the first web-based modeling tool that combines the tasks of creating, editing, running, and analyzing/visualizing stoichiometric models into a single program. Analysis results can be automatically superimposed on familiar KEGG-like maps. FAME is written in PHP and uses the Python-based PySCeS-CBM for its linear solving capabilities. It comes with a comprehensive manual and a quick-start tutorial, and can be accessed online at http://f-a-m-e.org/ .
• FASIMU — FASIMU is a command line oriented software implementing the most frequently applied FBA algorithms. It offers the first freely available implementation of (i) weighted flux minimization, (ii) fitness maximization for partially inhibited enzymes, and (iii) the concentration-based thermodynamic feasibility constraint. It allows heterogenous computation series suited for network pruning, leak analysis, FVA, and systematic probing of metabolic objectives for network curation controlled by an intuitive description file. The metabolic network can be supplied in SBML, CellNetAnalyzer, and plain text format. FASIMU uses the optimization capabilities of free (lp solve and GLPK) and commercial solvers (CPLEX, LINDO). The results can be visualized in Cytoscape or BiNA using newly developed plugins. The platform-independent program is an open-source project, freely available under GNU public license, including manual, tutorial, BiNA and Cytoscape plugin and respective manuals.
• FBASBW — A program allowing to define flux constraints using SBML annotations.
• Fluxor — Flux analysis. Free, part of BioSpice tool set. Linux.
• Genetic Network Analyzer — Genetic Network Analyzer (GNA) is a computer tool for the modeling, simulation, analysis and verification of genetic regulatory networks. The aim of GNA is to assist biologists and bioinformaticians in constructing a qualitative model of a genetic regulatory network from knowledge about regulatory interactions and gene expression data. GNA provides a variety of functions to analyze the steady-state and transient dynamics of the network, among other things by exploiting state-of-the-art model-checking tools.
• GINsim — GINsim is dedicated to the logical modelling of regulatory and signalling networks. It allows model definition and provides numerous functionalities for model analyses, including import and export facilities.
• GNU MCSim — GNU MCSim is a free standalone simulation package that allows you to design your own statistical or simulation models. It efficiently performs Bayesian inference through Markov Chain Monte Carlo simulations. Standard Monte Carlo and experimental design optimization are also available. GNU MCSim can import and simulate levels 1 and 2 SBML models
• iBioSim — The iBioSim tool supports the modeling, analysis, and design of genetic circuits with applications in both systems and synthetic biology. It includes editors to construct genetic circuit models (GCM), Systems Biology Markup Language (SBML) models (L2V4 and L3V1 supported), and labeled Petri net (LPN) models. Models can be constructed by hand, imported from model databases, or learned from experimental data. These models can be analyzed using a variety of ODE and stochastic simulators as well as Markov chain analysis. The efficiency of these analysis methods is enhanced using a variety of automatic reaction-based and logical abstractions. The analysis results can be plotted as graphs or visualized upon the genetic circuit schematic. (You can view the test results for this system in the SBML Test Suite Database.)
• IBRENA — To aid the analysis of complex biological reaction networks, we have developed a user-friendly program called “Insilico Biochemical REaction Network Analysis (IBRENA)”. This program is written in MATLABTM (The Mathworks, Inc., Natick, MA) with a Graphical User Interface (GUI). In order to reduce computation time, in some cases, ordinary differential equations (ODEs) are solved using Visual FORTRAN (HP-Compaq V6.6, Palo Alto, CA) with integrated IMSL library (Visual Numerics Inc., Houston, TX). This reduces the computational time required for time-consuming sensitivity analysis (described in Chapter 4 of the manual). This application can be deployed on a PC using Windows.
• 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.
• Jarnac — SBW tool for metabolic analysis, includes dynamic simulation. Simulation engine for JDesigner. BSD License.
• JigCell — JigCell is a set of computational tools with user-friendly interfaces developed for studying complex biochemical regulatory systems in general and the cell cycle control system in particular. For example, The JigCell Model Builder (JCMB) aides the modeler in defining a system to be modeled using SBML with a novel spreadsheet interface, allowing a large amount of data to be displayed in an organized manner. The JigCell Run Manager (JCRM) allows a user to specify a set of specifications for simulation runs using a spreadsheet interface. JigCell Aggregation Connector has been designed to define models in terms of components, for the purpose of being combined in a larger model. JigCell also aims in parameter estimation. A parameter estimator (PET, Parameter Estimation Toolkit) takes a biological model, experimental data, and the relationship between the model and data. Using this information the parameter estimator uses numerical tools to vary the parameters to the model looking for the parameters that best fit the experimental data.
• 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 supports model archive formats SBML (import and export) and CellML (import only).
• KEGGconverter — KEGGconverter automatically produces merged and converted to SBML fully functional pathway models, enhanced with default kinetics, by inputting only KGML files.The final derived models do not enclose trivial metabolites -reproducing inconsistencies of the KGML visualization-oriented, simplified information pattern- but at the same time they contain all the available information regarding the number of the included reactions in each pathway. Furthermore, additional reactions to neighbouring pathways are constructed which indicate the direction of the metabolic flows in the network and thus providing better stability in the boundary conditions of the models.
• MatCont — MatCont is a Matlab software package for the numerical study of parameterized continuous and discrete dynamical systems.
• MesoRD — MesoRD is a stochastic and deterministic simulator of coupled chemical reactions and diffusions in space.
• Metaboflux — Metaboflux is a computational tool for predicting flux distribution in metabolic networks under multiple and various constraints deducted from the experiments. It aims to increase the biological relevance of models by integrating experimental data. The tool is available in two versions : a command line tool optimized for running on HPC servers and a user-friendly interface designed to define model parameters and run simple computations. Metaboflux embedded a stochastic simulator of metabolic networks coupled with a non linear solver (GSL). It solves constraints defined as proportions (for example, metabolite proportions) or as equations. Results can be visualized directly in Metaboflux or within specific tools like Systrip.
• MetaFluxNet — MetaFluxNet is a program package for managing information on the metabolic reaction network and for quantitatively analyzing metabolic fluxes in an interactive and customized way, which allows users to interpret and examine metabolic behavior in response to genetic and/or environmental modifications. As a result, quantitative in silico simulations of metabolic pathways can be carried out to understand the metabolic status and to design the metabolic engineering strategies.
• MetExplore — A web server to link metabolic experiments and genome-scale metabolic networks. MetExplore contains original network filters, allows to export in SBML and visualise filtered metabolic networks, and map masses from metabolic experiments onto complete metabolic networks. It also contains some graph-based methods to enrich the analyses.
• MMT2 — Metabolic modeling, model fitting, automated high-performance code generation. (Linux only).
• modelMaGe — modelMaGe is a software application that a) automatically generates SBML or Copasi candidate models by removing specified model components from a given master model, b) automatically documents candidate models, c) automatically fits candidate models to data using CopasiSE, d) provides a ranking of candidate models fits based on the AIC.
• MOOSE — MOOSE 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 NeuroML.
• Odefy — Odefy is a MATLAB and Octave compatible toolbox which a modeling technique called HillCube, a canonical method to convert boolean models into continuous ordinary differential equation (ODE) systems. HillCubes are based on multivariate polynomial interpolation and incorporate Hill kinetics which are known to provide a good approximation of the synergistic dynamics of gene regulation.
• ONDEX — The Ondex data integration platform enables data from diverse biological data sets to be linked, integrated and visualised through graph analysis techniques. Ondex uses a rich and flexible core data structure, which has the ability to bring together information from structured databases and unstructured sources such as biological sequence data and free text. Ondex also allows users to visualise and analyse the integrated data.
• optflux — Simulation
• Pathway Analyser — Flux analysis. Free download, open source (Linux).
• PathwayLab — PathwayLab is a tool for modeling, analysis, and information management of biochemical pathways. It streamlines the pathway building process by a rich and flexible set of graphical building blocks for specifying biochemical entities, reaction, and control mechanisms. The pathway models are built using drag and drop from stencils into a workspace, which makes it very easy to rapidly build models of biochemical reaction networks such as signaling and metabolic pathways as well as gene regulatory networks. PathwayLab depends on Microsoft Visio.
• PET — Parameter optimization and exploration is the primary feature of PET. Some of the other tasks PET can perform are simulations, setting up multiple experiments for a model, comparing parameter sets, and exporting plots for presentations.
• PK-Sim / MoBi — Systems biology software platform for multiscale physiological modeling and simulation with a focus on physiologically-based pharmokinetics and -dynamics (PBPK/PD) including interfaces to MATLAB and R. Available to academic researchers via a free non-commercial license.
• PRISM — PRISM is a probabilistic model checker, a tool for formal verification of systems that exhibit stochastic behaviour. It supports construction and analysis of, amongst others, continuous-time Markov chains (CTMCs) and offers direct input from SBML models. PRISM performs exhaustive model analysis and computes exact values for a range of quantitative queries such as "what is the probability that ligand A eventually binds to protein B?" or "what is the expected amount of protein C at time T?".
• ProcessDB — ProcessDB helps molecular cell biologists manage and test their increasingly complex mechanistic hypotheses. ProcessDB does this with a bio-savvy graphical user interface that helps users formulate, visualize, compare, modify, manage and test their own mechanistic theories of cellular function. All models in ProcessDB can be automatically combined with user-specified experimental protocols and exported to the Berkeley Madonna solver for testing against experimental data. ProcessDB allows investigators to know with precision what their theories predict, and speeds discovery of mechanisms that account for all of the available data.
• PyDSTool — PyDSTool is a Python-based Dynamical Systems Toolkit. With PyDSTool we aim to provide a powerful suite of computational tools for the development, simulation, and analysis of dynamical systems that are used for the modeling of physical processes in many scientific disciplines, but especially in the biological sciences. We place emphasis on the support of data analysis and model fitting as a core part of the process of data-driven modeling. Our focus is on models involving ordinary differential equations (ODEs), differential-algebraic equations (DAEs), and discrete maps. Our approach differs from many existing software packages because of our focus on making model building, simulation, and analysis intuitive and efficient for an advanced end-user (who is unlikely to be either a mathematician or a computer programmer by trade) without sacrificing speed. We say for advanced users because PyDSTool does not provide a graphical interface, but instead a scripting environment with flexible, programmable library tools.
• PySCeS — PySCeS: the Python Simulator for Cellular Systems is an extendable toolkit for the analysis and investigation of cellular systems. PySCeS is developed in Python and has been designed to be used both interactively or as a library. It utilises a human readable, model description language for describing models as well as being SBML compatible. PySCeS includes stoichiometric, simulation, steady state and Eigen analysis using direct non-linear root finders. It also includes full support for Metabolic Control Analysis (MCA), the characterisation of static bifurcations, multidimensional parameter scanning and 2/3D graph capabilities. Currently an extension PySCeS-CBM is being developed that allows for the interactive manipulation, modelling and optimization of genome scale, constraint based models (e.g. flux balance analysis)
• SBML Harvester — The SBML Harvester creates a complex ontology-based representation of SBML models, utilizing both the structure of the SBML model and the models' MIRIAM annotations. This representation can then be used for the consistency verification of SBML models as well as complex queries across both models and biomedical ontologies.
• SBMLSim — Matlab GUI that allows the user to import a SBML model, simulate it, and visualize the simulations.
• SBSI — SBSI provides high performance fitting of model parameters to experimental data, with especial focus on models with oscillatory components. Additionally SBSI provides a modelling environment for the Bio-PEPA and Kappa languages, as well as standard model editing and simulation capabilities
• 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).
• 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)
• SensSB — A software toolbox for the development and sensitivity analysis of systems biology models
• SimBiology — SimBiology ® is a MATLAB ® product from MathWorks that provides graphical and programmatic tools for computational systems biology and pharmacokinetics. It contains functionality for creating, simulating, and analyzing biological models. The SimBiology desktop lets you build a model using a block diagram editor, a model wizard, or a tabular interface. You can also create a model at the command line or directly from SBML files. SimBiology lets you simulate a model using stochastic or deterministic solvers. The product supports parameter estimation, sensitivity analysis, parameter scans, and other model analysis methods. All SimBiology features can be used together with the MATLAB programming language, letting you customize models, create or modify analysis tasks, and automate your workflow.
• Simulation Core Library — Simulation Core Library is a fast, accurate, and easily usable program for dynamic simulation of models encoded in the Systems Biology Markup Language (SBML). In order to ensure a high reliability of this software, it has been benchmarked against the entire SBML Test Suite (all levels and versions) and all models from the Biomodels.net database. Simulation Core Library is included into SBMLsimulator, which includes a large collection of nature-inspired heuristic optimization procedures for efficient model calibration and provides an intuitive Graphical User Interface (GUI). Simulation Core Library runs on all platforms that provide a standard Java Virtual Machine and is based on the open-source library JSBML. (You can view the test results for this system in the SBML Test Suite Database.)
• Simulation Tool — The Simulation Tool is an environment for interactive exploration of SBML Models (L1-L3). It allows for simulation and analysis of models, provided capabilites (through simulators like RoadRunner) to define signals and events to interact with the model. Also features Steady State and Frequency Analysis.
• SloppyCell — SloppyCell is focused on parameter estimation and sensitivity analysis for ODE models. In particular, SloppyCell includes semi-analytic sensitivity integration, along with capability for building Bayesian ensembles of parameters sets consistent with given data.
• SOSlib — SOSlib is both a programming library and a command-line application for symbolic and numerical analysis of a system of ordinary differential equations (ODEs) derived from a chemical reaction network encoded in the Systems Biology Markup Language (SBML). It is written in ANSI/ISO C and distributed under the terms of the GNU Lesser General Public License (LGPL). The package employs libSBML's AST (Abstract Syntax Tree) for formula representation to construct ODE systems, their Jacobian matrix and other derivatives. CVODES, the sensitivity-enabled ODE solver in the SUNDIALS package is used for numerical integration and sensitivity analysis of stiff and non-stiff ODE systems. The native API provides fine-grained interfaces to all internal data structures, symbolic operations and numerical routines, enabling the construction of powerful and efficient analytic applications, hybrid solvers or multi-scale models with interfaces to non SBML data sources. Optional modules based on Graphviz and XMGrace allow a quick inspection of a model's structure and dynamics.
• SYCAMORE — SYCAMORE is a system that provides you with a faciliated access to a number of tools and methods in order to build models of biochemical systems, view, analyse and refine them, as well as perform quick simulations.
• Systrip — Systrip is a visual environment for the analysis of time-series data in the context of biological networks. This software gathers bioinformatics and graph theoretical algorithms that can be assembled in different ways to help biologists in their visual mining process. Main features : 1. SBML file import and export. 2. Multiple kind of metabolic network representations (3D, force directed, biological convention preserving, hierachical ...). 3. Both graph theoritical measures and metabolic network analysis algorithms (choke points, scope, centrality...). 4. Time-series data import and visualization (table view, parallel coordinates, scatter plot). 5. Visualization of time-series in the context of the metabolic network. 6. 3D molecular visualization. 7. Database querry tools (Kegg, PublicHouse).
• The Cell Collective — The Cell Collective allows laboratory scientists working in different areas of the cell to collectively integrate their knowledge and create large-scale (rule-based) computational models of biological/biochemical networks in a non-technical fashion. Models created in the Cell Collective can be published and made available to the whole community, or shared with a selected group of collaborators, or completely kept private. The software provides an environment not only for the construction and sharing of computational (rule-based) models, but also for real-time, interactive simulations, as well as automated experiments consisting of hundreds of simulations.
• 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.
• TinkerCell — TinkerCell is a drawing tool for synthetic biology that supports modular models and is highly extensible. One of the extensions is the COPASI C++ library, which adds most of the analysis capabilities from COPASI. Another extension support SBML import/export as well as the Antimony model definition language. TinkerCell supports over 200 Python and Octave functions, allowing users to add plug-ins written in Python or Octave. Users can also upload their plug-in to a central repository (hosted at Sourceforce); all other TinkerCell users will automatically get this plug-in in TinkerCell in the form of a new button. Hierarchical modeling is another key feature in TinkerCell, which is used in conjunction with a custom ontology for automatically generating one or more models from conceptual diagrams.
• VANTED — This system makes it possible to load and edit graphs, which may represent biological pathways or functional hierarchies. It is possible to map experimental datasets onto the graph elements and visualize time series data or data of different genotypes or environmental conditions in the context of a the underlying biological processes. Built-in statistic functions allow a fast evaluation of the data (e.g. t-Test or correlation analysis). Vanted can be extended for various functionalities, e.g. flux simulation, database access and 3D visualisation.
• WebCell — Online simulator, model builder, metabolic controal analysis. Includes database of bimodels and JWS models. Registration required.
• WinSCAMP — Windows Binary for SCAMP. Metabolic analysis, ODE solver. Binary download only. Source code on request.
• Wolfram SystemModeler — Wolfram SystemModeler is a high-fidelity modeling software based on the Modelica language. It allows for hierarchical, multidomain, and hybrid systems modeling using a graphical drag and drop environment, and/or an equation based textual interface. And it integrates with the Wolfram technology platform to enable modeling, simulation, and analysis (of many types), all together achieving an agile design optimization loop. Provided with SystemModeler is a large set of built-in model libraries, including the BioChem library - an SBML compatible Modelica library designed for biochemical systems. By making use of the BioChem library, SystemModeler lets you build, simulate, and visualize PKPD and systems biology models. The software also provides SBML import and export functionality to allow Modelica-SBML model exchange.

• CellDesigner — CellDesigner is a structured diagram editor for drawing gene-regulatory and biochemical networks. Networks are drawn based on the process diagram, with graphical notation system. CellDesigner supports simulation and parameter scan by an integration with SBML ODE Solver and Copasi. By using CellDesigner, users can browse and modify existing SBML models with references to existing databases (MIRIAM supported), simulate and view the dynamics through an intuitive graphical interface.
• COPASI — COPASI is a software application for simulation and analysis of biochemical networks and their dynamics. COPASI is a stand-alone program that supports models in the SBML standard and can simulate their behavior using ODEs or Gillespie's stochastic simulation algorithm; arbitrary discrete events can be included in such simulations. COPASI provides an C++ API with language bindings for Perl, python, R, Java, and Octave and is able to communicate with the Systems Biology Workbench COPASI carries out several analyses of the network and its dynamics and has extensive support for parameter estimation and optimization. COPASI provides means to visualize data in customizable plots, histograms and animations of network diagrams. Please see the COPASI detailed description for a complete list of features. (You can view the test results for this system in the SBML Test Suite Database.)
• CySBML — Summary: CySBML is a plugin for the work with SBML in Cytoscape having the following features: SBML import, support of the SBML Layout and Qualitative Model packages, navigation in network layouts based on SBML structure, access to MIRIAM and SBO-based annotations, and SBML validation. CySBML includes an importer for BioModels to load SBML from standard repositories. Availability and implementation: Freely available for non-commercial purposes via the Cytoscape plugin manager or for download at http://sourceforge.net/projects/cysbml/. Main purpose is an import of SBML with the semantic annotations available within the Cytoscape network visualization.
• GNAT — GNAT is an open source MATLAB-based toolbox. It provides functions for reading, writing, manipulation, visualization and simulation of glycan structures and glycosylation reaction networks. It is written in MATLAB and Java. It is thus platform-independent. It has been tested in Windows (Windows 7), Linux (Ubuntu), and Mac OS (X Lion) platforms.
• KEGGtranslator — Nowadays, the KEGG PATHWAY database provides a widely used service for pathway-based information. It contains manually drawn pathway maps with information about the genes, reactions and relations contained therein. To store these pathways, KEGG uses an own XML-format (called “KGML”). Parsers and translators are needed to process the pathway maps for usage in other applications and algorithms. We have developed KEGGtranslator, which is an easy-to-use stand-alone application that can visualize and convert KGML formatted XML-files into multiple output formats. Unlike other translators, KEGGtranslator supports a plethora of output formats, is able to augment the information in translated documents (e.g., MIRIAM annotations) beyond the scope of the KGML document, and amends missing components to fragmentary reactions within the pathway to allow simulations on those. KEGGtranslator converts KEGG files (KGML formatted XML-files) to SBML, GML, GraphML, JPG, GIF, LaTeX, etc. KEGG pathways can be obtained from ftp://ftp.genome.jp/pub/kegg/xml/kgml
• Metannogen — Metannogen is used to browse and annotate existing biological networks given in SBML. It can work together with any network editor that creates SBML files. Its capability of communication with other programs via network sockets allows embedding as a module within other software. It can also be used for network reconstruction to create a network from scratch.
• PAYAO — PAYAO is a community collaborative web service platform for gene-regulatory and biochemical pathway model curation.
• PK-Sim / MoBi — Systems biology software platform for multiscale physiological modeling and simulation with a focus on physiologically-based pharmokinetics and -dynamics (PBPK/PD) including interfaces to MATLAB and R. Available to academic researchers via a free non-commercial license.
• 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.
• SBMLEditor — SBMLeditor a very simple, low level editor of SBML files. Users can create and remove all the necessary bits and pieces of SBML in a controlled way, that maintains the validity and consistency of the final SBML file
• SBMLsqueezer — SBMLsqueezer generates kinetic equations for biochemical networks according to context of each reaction. When used as a plug-in for CellDesigner it uses the information from the SBGN representation of all network components. In the stand-alone mode, SBMLsqueezer evaluates the Systems Biology Ontology (SBO) annotations to extract this information. An online version of SBMLsqueezer is available that runs without instally any software on the local machine. The rate laws that can be produced by SBMLsqueezer include several types of generalized mass action; detailed and generalized enzyme kinetics, various types of Hill equations, S- and H-systems, and additive models for gene regulation. User defined settings specify which equation to apply for any type of reaction and how to ensure unit consistency of the model. Equations can be created using contextual menus. All newly created parameters are equipped with the derived unit and annotated with SBO terms if available and meaningful textual names. MathML is inserted directly into the SBML file. LaTeX or text export of ordinary differential equations is provided.
• 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)
• semanticSBML — Create, check, visualize, retrieve, cluster, annotate, merge SBML models. The program includes a web based graphical user interface. For tool developers a programming interface (Python) and RESTful web-services are provided. It features advanced functions to edit MIRIAM and SBO terms. The latest version of semanticSBML is fully web based and can be accessed under http://semanticsbml.org/semanticSBML/simple/index
• SurreyFBA — SurreyFBA provides constraint-based simulations of genome scale metabolic networks in a free, stand-alone software. In addition to basic simulation protocols the tool also implements the analysis of minimal substrate and product sets, which is useful for metabolic engineering and prediction of nutritional requirements in complex in vivo environments. The SurreyFBA is based on a command line interface to the GLPK solver distributed as binary and source code for the three major operating systems. The sfba command line tool, implemented in C++, is easily executed within scripting languages used in the bioinformatics community and provides efficient implementation of tasks requiring iterative calls to the linear programming solver. SurreyFBA includes JyMet, a graphics user interface allowing spreadsheet based model presentation, visualization of numerical results on metabolic networks represented in the Petri net convention, as well as in charts and plots.

• 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.
• AMIGO — AMIGO means Advanced Model Identification using Global Optimization. AMIGO is a multi-platform (Windows and Linux) matlab-bsed toolbox which covers all the steps of system identification in systems biology. This includes: local and global sensitivity analysis, local and global ranking of parameters, parameter estimation, identifiability analysis and optimal experimental design.
• 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.
• APMonitor — The APMonitor Modeling Language is optimization software for differential and algebraic equations. It is coupled with large-scale nonlinear programming solvers for data reconciliation, real-time optimization, dynamic simulation, and nonlinear predictive control. It is available as a free web service through MATLAB or Python.
• Asmparts — Produces models of biological systems by assembling models from biological parts.
• Athena — Athena is a graphical modeling tool experimenting with modular systems. Athena is integrated with SBW and allows the analysis of models through a multitude of plugins. It is available for windows only, and released under the BSD license.
• BALSA — Front end for Sigtran (inactive?)
• Bio Sketch Pad — graphical model design tool, front end for BioCharon
• BioCharon — 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.
• Biological Networks — 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)
• 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.
• BioUML — platform for building virtual cell and virtual physiological human. (You can view the test results for this system in the SBML Test Suite Database.)
• CARMEN — CARMEN provides the KGML-based model generation of metabolic pathways based on KEGG database information and the application of template-based models for comparative genomics. This software will be of interest in genome sequencing projects aiming at the rapid analysis and visualization of microbial metabolic features. The KGML-based model generation facilitates a high-speed generated overview of the metabolic repertoire. The comparative analysis of newly sequenced organisms is highly desirable to identify organism-specific features. The reconstructed networks are stored in standardized SBML format.
• Cell Illustrator — Graphical model editor; Petri-net based simulation algorithm; SBML Import. Commercial. (Linux/Mac/Win).
• CellDesigner — CellDesigner is a structured diagram editor for drawing gene-regulatory and biochemical networks. Networks are drawn based on the process diagram, with graphical notation system. CellDesigner supports simulation and parameter scan by an integration with SBML ODE Solver and Copasi. By using CellDesigner, users can browse and modify existing SBML models with references to existing databases (MIRIAM supported), simulate and view the dynamics through an intuitive graphical interface.
• Cellerator — Cellerator describes single and multi-cellular signal transduction networks (STN) with a compact, optionally palette-driven, arrow-based notation to represent biochemical reactions and transcriptional activation. Multi-compartment systems are represented as graphs with STNs embedded in each node. Interactions include mass-action, enzymatic, allosteric and connectionist models. Reactions are translated into differential equations and can be solved numerically to generate predictive time courses or output as systems of equations that can be read by other programs. Cellerator simulations are fully extensible and portable to any operating system that supports Mathematica, and can be indefinitely nested within larger data structures to produce highly scaleable models.. Cellerator is superseeded by xCellerator.
• COPASI — COPASI is a software application for simulation and analysis of biochemical networks and their dynamics. COPASI is a stand-alone program that supports models in the SBML standard and can simulate their behavior using ODEs or Gillespie's stochastic simulation algorithm; arbitrary discrete events can be included in such simulations. COPASI provides an C++ API with language bindings for Perl, python, R, Java, and Octave and is able to communicate with the Systems Biology Workbench COPASI carries out several analyses of the network and its dynamics and has extensive support for parameter estimation and optimization. COPASI provides means to visualize data in customizable plots, histograms and animations of network diagrams. Please see the COPASI detailed description for a complete list of features. (You can view the test results for this system in the SBML Test Suite Database.)
• DBSolve — DBSolveOptimum is a free software for kinetic modeling of metabolic pathways, analysis, and fitting parameters to experimental data. The program has text-based user interface for model description and graphical interface for data analysis. In addition to standart algorithms of simulation (ODE solver, explicit solver, steady-state analysis) the software include also automated local sencetivity analysis, parameters optimization procedures and bifurcaion analysis. The last version of DBSolveOptimum includes advanced tool for data visualization.
• Facile — Facile / EasyStoch. A command-line network compiler for systems biology. Facile reads models given in a simple and human-readable textual input format and exports the model in a format for readable by Matlab, Mathematica, Maple, XPP/AUTO. Other tools are supported via SBML export. For stochastic simulations, Facile uses the EasyStoch stochastic simulator. An important feature of EasyStoch that distinguishes it from other Gillespie-algorithm implementations is that it is capable of simulating dynamically changing or noisy biochemical parameters (i.e. extrinsic noise).
• FAME — The Flux Analysis and Modeling Environment (FAME) is the first web-based modeling tool that combines the tasks of creating, editing, running, and analyzing/visualizing stoichiometric models into a single program. Analysis results can be automatically superimposed on familiar KEGG-like maps. FAME is written in PHP and uses the Python-based PySCeS-CBM for its linear solving capabilities. It comes with a comprehensive manual and a quick-start tutorial, and can be accessed online at http://f-a-m-e.org/ .
• Genetic Network Analyzer — Genetic Network Analyzer (GNA) is a computer tool for the modeling, simulation, analysis and verification of genetic regulatory networks. The aim of GNA is to assist biologists and bioinformaticians in constructing a qualitative model of a genetic regulatory network from knowledge about regulatory interactions and gene expression data. GNA provides a variety of functions to analyze the steady-state and transient dynamics of the network, among other things by exploiting state-of-the-art model-checking tools.
• GNU MCSim — GNU MCSim is a free standalone simulation package that allows you to design your own statistical or simulation models. It efficiently performs Bayesian inference through Markov Chain Monte Carlo simulations. Standard Monte Carlo and experimental design optimization are also available. GNU MCSim can import and simulate levels 1 and 2 SBML models
• HSMB — Hybrid SBML Model Builder for BioCharon.
• HybridSBML — Hybrid SBML Model Builder for BioCharon
• iBioSim — The iBioSim tool supports the modeling, analysis, and design of genetic circuits with applications in both systems and synthetic biology. It includes editors to construct genetic circuit models (GCM), Systems Biology Markup Language (SBML) models (L2V4 and L3V1 supported), and labeled Petri net (LPN) models. Models can be constructed by hand, imported from model databases, or learned from experimental data. These models can be analyzed using a variety of ODE and stochastic simulators as well as Markov chain analysis. The efficiency of these analysis methods is enhanced using a variety of automatic reaction-based and logical abstractions. The analysis results can be plotted as graphs or visualized upon the genetic circuit schematic. (You can view the test results for this system in the SBML Test Suite Database.)
• insilicoIDE — insilicoIDE (ISIDE) assists users to build models of physiological functions with multilevel hierarchical structure and to run simulations. A model is built as a functional network of "modules" which represent physiological entities. In each module, equations such as ODEs and PDEs, parameters and morphological information can be defined. Besides, a module can include a model written in SBML. The SBML model is functionally embedded in the module network. There is an open model database at www.physiome.jp. Users can use models in the database freely as parts to build their own model. The modularity of the model representation in ISIDE makes reuse and integration of multiple models easier. The simulator included in ISIDE supports parallel computing.
• JACOBIAN — numerical engine underlying OpenBio
• Jarnac — SBW tool for metabolic analysis, includes dynamic simulation. Simulation engine for JDesigner. BSD License.
• JarnacLite — JarnacLite allows to edit SBML through a simple script based format. It is integrated with SBW, so that a model created with JarnacLite can be quickly simulated and analyzed with a variety of tools. JarnacLite is available on all platforms, and as translator also online. It is released under the BSD license.
• JDesigner — Graphical model design tool. Typically uses RoadRunner as a simulation engine via SBW. Free/Open Source (BSD).
• JigCell — JigCell is a set of computational tools with user-friendly interfaces developed for studying complex biochemical regulatory systems in general and the cell cycle control system in particular. For example, The JigCell Model Builder (JCMB) aides the modeler in defining a system to be modeled using SBML with a novel spreadsheet interface, allowing a large amount of data to be displayed in an organized manner. The JigCell Run Manager (JCRM) allows a user to specify a set of specifications for simulation runs using a spreadsheet interface. JigCell Aggregation Connector has been designed to define models in terms of components, for the purpose of being combined in a larger model. JigCell also aims in parameter estimation. A parameter estimator (PET, Parameter Estimation Toolkit) takes a biological model, experimental data, and the relationship between the model and data. Using this information the parameter estimator uses numerical tools to vary the parameters to the model looking for the parameters that best fit the experimental data.
• 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 supports model archive formats SBML (import and export) and CellML (import only).
• 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.
• KEGGtranslator — Nowadays, the KEGG PATHWAY database provides a widely used service for pathway-based information. It contains manually drawn pathway maps with information about the genes, reactions and relations contained therein. To store these pathways, KEGG uses an own XML-format (called “KGML”). Parsers and translators are needed to process the pathway maps for usage in other applications and algorithms. We have developed KEGGtranslator, which is an easy-to-use stand-alone application that can visualize and convert KGML formatted XML-files into multiple output formats. Unlike other translators, KEGGtranslator supports a plethora of output formats, is able to augment the information in translated documents (e.g., MIRIAM annotations) beyond the scope of the KGML document, and amends missing components to fragmentary reactions within the pathway to allow simulations on those. KEGGtranslator converts KEGG files (KGML formatted XML-files) to SBML, GML, GraphML, JPG, GIF, LaTeX, etc. KEGG pathways can be obtained from ftp://ftp.genome.jp/pub/kegg/xml/kgml
• MEMOSys — MEMOSys is a versatile platform for the management, storage, and development of genome-scale metabolic models. It supports the development of new models by providing a built-in version control system which offers access to the complete developmental history. Moreover, the integrated web board, the authorization system, and the definition of user roles allow collaborations across departments and institutions. Research on existing models is facilitated by a search system, references to external databases, and a feature-rich comparison mechanism. MEMOSys provides customizable data exchange mechanisms using the SBML format to enable analysis in external tools. It currently contains 9 annotated microbial metabolic models.
• MetaFluxNet — MetaFluxNet is a program package for managing information on the metabolic reaction network and for quantitatively analyzing metabolic fluxes in an interactive and customized way, which allows users to interpret and examine metabolic behavior in response to genetic and/or environmental modifications. As a result, quantitative in silico simulations of metabolic pathways can be carried out to understand the metabolic status and to design the metabolic engineering strategies.
• MetNetMaker — MetNetMaker is the simplest way to create SBML-format metabolic models based on the KEGG LIGAND ontology. Models can be visualised in Cytoscape and are ready for FBA using the COBRA toolbox.
• modelMaGe — modelMaGe is a software application that a) automatically generates SBML or Copasi candidate models by removing specified model components from a given master model, b) automatically documents candidate models, c) automatically fits candidate models to data using CopasiSE, d) provides a ranking of candidate models fits based on the AIC.
• Monod — "Modeler's Notebook and Data Store" model annotation manager. (Linux/Mac OS) Open Source, Must build from source (LGPL).
• NetBuilder' — NetBuilder' is a software tool that is intended to help experimentalists creating and manipulating the mathematical representations they need to predict the behaviour of their systems. NetBuilder' has a graphical user interface, which allows its users to create a picture of the (known) components and interactions in the system, and enter quantitative information, such as know or estimated quantities and rates. A (hidden) translator converts the picture and the other data into a mathematical description, whereupon NetBuilder's "simulation engine" may be used to find out how the modelled system responds to changing input.
• Pathway Builder — Graphical model design. Part of Bio-Spice. (BioSpice BSD License)
• PathwayLab — PathwayLab is a tool for modeling, analysis, and information management of biochemical pathways. It streamlines the pathway building process by a rich and flexible set of graphical building blocks for specifying biochemical entities, reaction, and control mechanisms. The pathway models are built using drag and drop from stencils into a workspace, which makes it very easy to rapidly build models of biochemical reaction networks such as signaling and metabolic pathways as well as gene regulatory networks. PathwayLab depends on Microsoft Visio.
• PK-Sim / MoBi — Systems biology software platform for multiscale physiological modeling and simulation with a focus on physiologically-based pharmokinetics and -dynamics (PBPK/PD) including interfaces to MATLAB and R. Available to academic researchers via a free non-commercial license.
• ProcessDB — ProcessDB helps molecular cell biologists manage and test their increasingly complex mechanistic hypotheses. ProcessDB does this with a bio-savvy graphical user interface that helps users formulate, visualize, compare, modify, manage and test their own mechanistic theories of cellular function. All models in ProcessDB can be automatically combined with user-specified experimental protocols and exported to the Berkeley Madonna solver for testing against experimental data. ProcessDB allows investigators to know with precision what their theories predict, and speeds discovery of mechanisms that account for all of the available data.
• ProMoT — The process modeling tool ProMoT is a software for the set-up and manipulation of models of complex technical or biological systems. Key features are the support of modular models, modeling libraries for different application areas, efficient and robust numerical algorithms, a own modeling language MDL 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.
• PyDSTool — PyDSTool is a Python-based Dynamical Systems Toolkit. With PyDSTool we aim to provide a powerful suite of computational tools for the development, simulation, and analysis of dynamical systems that are used for the modeling of physical processes in many scientific disciplines, but especially in the biological sciences. We place emphasis on the support of data analysis and model fitting as a core part of the process of data-driven modeling. Our focus is on models involving ordinary differential equations (ODEs), differential-algebraic equations (DAEs), and discrete maps. Our approach differs from many existing software packages because of our focus on making model building, simulation, and analysis intuitive and efficient for an advanced end-user (who is unlikely to be either a mathematician or a computer programmer by trade) without sacrificing speed. We say for advanced users because PyDSTool does not provide a graphical interface, but instead a scripting environment with flexible, programmable library tools.
• 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.
• SBML2NEURON — SBML2NEURON is a provisional implementation of an SBML to NEURON converter. This uses the Python bindings of libSBML to generate an NMODL file containing the model represented in a basic SBML file, which can then be inserted onto a section in NEURON for simulation. Note that only a restricted set of SBML elements are supported (see the notes), but it can be used to simulate some of the models in BioModels Database. This is a work in progress and will be developed further to allow closer integration between NeuroML and SBML in realistic neuronal models.
• SBMLEditor — SBMLeditor a very simple, low level editor of SBML files. Users can create and remove all the necessary bits and pieces of SBML in a controlled way, that maintains the validity and consistency of the final SBML file
• SBML-shorthand — Specification and conversion tools for a simple human-readable shorthand notation for a subset of SBML. Used for rapid building of SBML models without using a sophisticated GUI tool.
• SBMLsqueezer — SBMLsqueezer generates kinetic equations for biochemical networks according to context of each reaction. When used as a plug-in for CellDesigner it uses the information from the SBGN representation of all network components. In the stand-alone mode, SBMLsqueezer evaluates the Systems Biology Ontology (SBO) annotations to extract this information. An online version of SBMLsqueezer is available that runs without instally any software on the local machine. The rate laws that can be produced by SBMLsqueezer include several types of generalized mass action; detailed and generalized enzyme kinetics, various types of Hill equations, S- and H-systems, and additive models for gene regulation. User defined settings specify which equation to apply for any type of reaction and how to ensure unit consistency of the model. Equations can be created using contextual menus. All newly created parameters are equipped with the derived unit and annotated with SBO terms if available and meaningful textual names. MathML is inserted directly into the SBML file. LaTeX or text export of ordinary differential equations is provided.
• SBMLToolbox — Manipulation of SBML in both the MATLAB and Octave environments. Some simulation support but the main focus is on allowing users to adapt SBML to their existing MATLAB/Octave functions. (You can view the test results for this system in the SBML Test Suite Database.)
• 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)
• SED-ML Web Tools — The SED-ML Web tools represent a suite of tools for creating, editing, simulating and validating SED-ML files.SED-ML descriptions can be created directly by uploading an SBML model.
• semanticSBML — Create, check, visualize, retrieve, cluster, annotate, merge SBML models. The program includes a web based graphical user interface. For tool developers a programming interface (Python) and RESTful web-services are provided. It features advanced functions to edit MIRIAM and SBO terms. The latest version of semanticSBML is fully web based and can be accessed under http://semanticsbml.org/semanticSBML/simple/index
• SigTran — SigTran is a modeling environment especially designed to enable biological researchers to carry out large scale simulations and analysis of complex signal transduction networks. (inactive?)
• SimBiology — SimBiology ® is a MATLAB ® product from MathWorks that provides graphical and programmatic tools for computational systems biology and pharmacokinetics. It contains functionality for creating, simulating, and analyzing biological models. The SimBiology desktop lets you build a model using a block diagram editor, a model wizard, or a tabular interface. You can also create a model at the command line or directly from SBML files. SimBiology lets you simulate a model using stochastic or deterministic solvers. The product supports parameter estimation, sensitivity analysis, parameter scans, and other model analysis methods. All SimBiology features can be used together with the MATLAB programming language, letting you customize models, create or modify analysis tasks, and automate your workflow.
• The Cell Collective — The Cell Collective allows laboratory scientists working in different areas of the cell to collectively integrate their knowledge and create large-scale (rule-based) computational models of biological/biochemical networks in a non-technical fashion. Models created in the Cell Collective can be published and made available to the whole community, or shared with a selected group of collaborators, or completely kept private. The software provides an environment not only for the construction and sharing of computational (rule-based) models, but also for real-time, interactive simulations, as well as automated experiments consisting of hundreds of simulations.
• TinkerCell — TinkerCell is a drawing tool for synthetic biology that supports modular models and is highly extensible. One of the extensions is the COPASI C++ library, which adds most of the analysis capabilities from COPASI. Another extension support SBML import/export as well as the Antimony model definition language. TinkerCell supports over 200 Python and Octave functions, allowing users to add plug-ins written in Python or Octave. Users can also upload their plug-in to a central repository (hosted at Sourceforce); all other TinkerCell users will automatically get this plug-in in TinkerCell in the form of a new button. Hierarchical modeling is another key feature in TinkerCell, which is used in conjunction with a custom ontology for automatically generating one or more models from conceptual diagrams.
• Wolfram SystemModeler — Wolfram SystemModeler is a high-fidelity modeling software based on the Modelica language. It allows for hierarchical, multidomain, and hybrid systems modeling using a graphical drag and drop environment, and/or an equation based textual interface. And it integrates with the Wolfram technology platform to enable modeling, simulation, and analysis (of many types), all together achieving an agile design optimization loop. Provided with SystemModeler is a large set of built-in model libraries, including the BioChem library - an SBML compatible Modelica library designed for biochemical systems. By making use of the BioChem library, SystemModeler lets you build, simulate, and visualize PKPD and systems biology models. The software also provides SBML import and export functionality to allow Modelica-SBML model exchange.

• AMIGO — AMIGO means Advanced Model Identification using Global Optimization. AMIGO is a multi-platform (Windows and Linux) matlab-bsed toolbox which covers all the steps of system identification in systems biology. This includes: local and global sensitivity analysis, local and global ranking of parameters, parameter estimation, identifiability analysis and optimal experimental design.
• 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.
• CADLIVE — CADLIVE (Computer-Aided Design of LIVing systEms) is a comprehensive computational tool for constructing large-scale biological network maps, analyzing the topological features of them, and simulating their dynamics. Using CADLIVE, we rationally design a biological system at the molecular interaction level for an engineering purpose.
• CARMEN — CARMEN provides the KGML-based model generation of metabolic pathways based on KEGG database information and the application of template-based models for comparative genomics. This software will be of interest in genome sequencing projects aiming at the rapid analysis and visualization of microbial metabolic features. The KGML-based model generation facilitates a high-speed generated overview of the metabolic repertoire. The comparative analysis of newly sequenced organisms is highly desirable to identify organism-specific features. The reconstructed networks are stored in standardized SBML format.
• CySBML — Summary: CySBML is a plugin for the work with SBML in Cytoscape having the following features: SBML import, support of the SBML Layout and Qualitative Model packages, navigation in network layouts based on SBML structure, access to MIRIAM and SBO-based annotations, and SBML validation. CySBML includes an importer for BioModels to load SBML from standard repositories. Availability and implementation: Freely available for non-commercial purposes via the Cytoscape plugin manager or for download at http://sourceforge.net/projects/cysbml/. Main purpose is an import of SBML with the semantic annotations available within the Cytoscape network visualization.
• Insilico Discovery — modeling and simulation platform for graphically oriented setup, management and engineering of cellular networks
• insilicoIDE — insilicoIDE (ISIDE) assists users to build models of physiological functions with multilevel hierarchical structure and to run simulations. A model is built as a functional network of "modules" which represent physiological entities. In each module, equations such as ODEs and PDEs, parameters and morphological information can be defined. Besides, a module can include a model written in SBML. The SBML model is functionally embedded in the module network. There is an open model database at www.physiome.jp. Users can use models in the database freely as parts to build their own model. The modularity of the model representation in ISIDE makes reuse and integration of multiple models easier. The simulator included in ISIDE supports parallel computing.
• 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 supports model archive formats SBML (import and export) and CellML (import only).
• KEGGconverter — KEGGconverter automatically produces merged and converted to SBML fully functional pathway models, enhanced with default kinetics, by inputting only KGML files.The final derived models do not enclose trivial metabolites -reproducing inconsistencies of the KGML visualization-oriented, simplified information pattern- but at the same time they contain all the available information regarding the number of the included reactions in each pathway. Furthermore, additional reactions to neighbouring pathways are constructed which indicate the direction of the metabolic flows in the network and thus providing better stability in the boundary conditions of the models.
• KEGGtranslator — Nowadays, the KEGG PATHWAY database provides a widely used service for pathway-based information. It contains manually drawn pathway maps with information about the genes, reactions and relations contained therein. To store these pathways, KEGG uses an own XML-format (called “KGML”). Parsers and translators are needed to process the pathway maps for usage in other applications and algorithms. We have developed KEGGtranslator, which is an easy-to-use stand-alone application that can visualize and convert KGML formatted XML-files into multiple output formats. Unlike other translators, KEGGtranslator supports a plethora of output formats, is able to augment the information in translated documents (e.g., MIRIAM annotations) beyond the scope of the KGML document, and amends missing components to fragmentary reactions within the pathway to allow simulations on those. KEGGtranslator converts KEGG files (KGML formatted XML-files) to SBML, GML, GraphML, JPG, GIF, LaTeX, etc. KEGG pathways can be obtained from ftp://ftp.genome.jp/pub/kegg/xml/kgml
• Medicel — commercial data integration framework. (now euformatics)
• MEMOSys — MEMOSys is a versatile platform for the management, storage, and development of genome-scale metabolic models. It supports the development of new models by providing a built-in version control system which offers access to the complete developmental history. Moreover, the integrated web board, the authorization system, and the definition of user roles allow collaborations across departments and institutions. Research on existing models is facilitated by a search system, references to external databases, and a feature-rich comparison mechanism. MEMOSys provides customizable data exchange mechanisms using the SBML format to enable analysis in external tools. It currently contains 9 annotated microbial metabolic models.
• MetaCrop — MetaCrop is a database that contains manually curated, highly detailed information about metabolic pathways in crop plants, including location information, transport processes, and reaction kinetics. The web interface supports an easy exploration of the information from overview pathways to single reactions and therefore helps users understanding the metabolism of crop plants. It also allows automatic data export for the creation of detailed models of metabolic pathways to support simulation approaches.
• Metannogen — Metannogen is used to browse and annotate existing biological networks given in SBML. It can work together with any network editor that creates SBML files. Its capability of communication with other programs via network sockets allows embedding as a module within other software. It can also be used for network reconstruction to create a network from scratch.
• MIRIAM Resources — a set of online services created in support of MIRIAM, a set of guidelines for the annotation and curation of computational models.
• ONDEX — The Ondex data integration platform enables data from diverse biological data sets to be linked, integrated and visualised through graph analysis techniques. Ondex uses a rich and flexible core data structure, which has the ability to bring together information from structured databases and unstructured sources such as biological sequence data and free text. Ondex also allows users to visualise and analyse the integrated data.
• Pathway Access — PathwayAccess is a suite of CellDesigner plugins which directly interact with pathway datasources
• Pathway Tools — Extracts and integrates information from pathway/genome databases (see 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).
• PATIKAweb — Pathway database integration; pathway visualization and analysis. Online tool only. (Acad/NP)
• PK-Sim / MoBi — Systems biology software platform for multiscale physiological modeling and simulation with a focus on physiologically-based pharmokinetics and -dynamics (PBPK/PD) including interfaces to MATLAB and R. Available to academic researchers via a free non-commercial license.
• ProcessDB — ProcessDB helps molecular cell biologists manage and test their increasingly complex mechanistic hypotheses. ProcessDB does this with a bio-savvy graphical user interface that helps users formulate, visualize, compare, modify, manage and test their own mechanistic theories of cellular function. All models in ProcessDB can be automatically combined with user-specified experimental protocols and exported to the Berkeley Madonna solver for testing against experimental data. ProcessDB allows investigators to know with precision what their theories predict, and speeds discovery of mechanisms that account for all of the available data.
• 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
• SABIO-RK — SABIO-RK is a curated database for biochemical reaction kinetics data. The data is drawn from different sources: by extraction from published literature or direct submission by experimenters, and is supplemented with additional data from other databases. The system offers standardized data by the use of controlled vocabularies and annotations pointing to other resources and biological ontologies. It can be accessed either manually via a web-based search interface or automatically via web services that allow direct data access by other tools. Both interfaces support the export of the data together with its annotations in SBML. SABIO-RK facilitates the exchange of kinetic data between experimentalists and modellers, and thereby supports the setup of quantitative computer models.
• 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.
• SBML Harvester — The SBML Harvester creates a complex ontology-based representation of SBML models, utilizing both the structure of the SBML model and the models' MIRIAM annotations. This representation can then be used for the consistency verification of SBML models as well as complex queries across both models and biomedical ontologies.
• SBMM assistant — Systems Biology Metabolic Modeling assistant (SBMM assistant) is a web application to consult basic metabolic information, to build metabolic models, and to annotate them in SBML files with external resource annotations suggested by MIRIAM
• SBO — The Systems Biology Ontology is a set of controlled, relational vocabularies of terms commonly used in Systems Biology, and in particular in computational modeling.
• SCIpath — microarray data management. (Linux/Windows).
• semanticSBML — Create, check, visualize, retrieve, cluster, annotate, merge SBML models. The program includes a web based graphical user interface. For tool developers a programming interface (Python) and RESTful web-services are provided. It features advanced functions to edit MIRIAM and SBO terms. The latest version of semanticSBML is fully web based and can be accessed under http://semanticsbml.org/semanticSBML/simple/index
• SIGNALIGN — online pathway alignment service.
• SignaLink — SignaLink is a multi-layered (onion-like) database made up of signaling pathways, their pathway regulators (e.g., scaffold and endocytotic proteins) and modifier enzymes (e.g., phosphatases, ubiquitin ligases), as well as transcriptional and post-transcriptional regulators of all of these components. The user-friendly website allows the interactive exploration of how each signaling protein is regulated. The customizable download page enables the analysis of any user-specified part of the signaling network of human and two invertebrate model organisms, C. elegans and D. melanogaster.
• SigPath — Bioinformatic database and pathway management (GPL).
• SimBiology — SimBiology ® is a MATLAB ® product from MathWorks that provides graphical and programmatic tools for computational systems biology and pharmacokinetics. It contains functionality for creating, simulating, and analyzing biological models. The SimBiology desktop lets you build a model using a block diagram editor, a model wizard, or a tabular interface. You can also create a model at the command line or directly from SBML files. SimBiology lets you simulate a model using stochastic or deterministic solvers. The product supports parameter estimation, sensitivity analysis, parameter scans, and other model analysis methods. All SimBiology features can be used together with the MATLAB programming language, letting you customize models, create or modify analysis tasks, and automate your workflow.
• SRS — Data integration for bioinformatics. Commercial.
• SYCAMORE — SYCAMORE is a system that provides you with a faciliated access to a number of tools and methods in order to build models of biochemical systems, view, analyse and refine them, as well as perform quick simulations.
• The Cell Collective — The Cell Collective allows laboratory scientists working in different areas of the cell to collectively integrate their knowledge and create large-scale (rule-based) computational models of biological/biochemical networks in a non-technical fashion. Models created in the Cell Collective can be published and made available to the whole community, or shared with a selected group of collaborators, or completely kept private. The software provides an environment not only for the construction and sharing of computational (rule-based) models, but also for real-time, interactive simulations, as well as automated experiments consisting of hundreds of simulations.
• VANTED — This system makes it possible to load and edit graphs, which may represent biological pathways or functional hierarchies. It is possible to map experimental datasets onto the graph elements and visualize time series data or data of different genotypes or environmental conditions in the context of a the underlying biological processes. Built-in statistic functions allow a fast evaluation of the data (e.g. t-Test or correlation analysis). Vanted can be extended for various functionalities, e.g. flux simulation, database access and 3D visualisation.

• AMIGO — AMIGO means Advanced Model Identification using Global Optimization. AMIGO is a multi-platform (Windows and Linux) matlab-bsed toolbox which covers all the steps of system identification in systems biology. This includes: local and global sensitivity analysis, local and global ranking of parameters, parameter estimation, identifiability analysis and optimal experimental design.
• APMonitor — The APMonitor Modeling Language is optimization software for differential and algebraic equations. It is coupled with large-scale nonlinear programming solvers for data reconciliation, real-time optimization, dynamic simulation, and nonlinear predictive control. It is available as a free web service through MATLAB or Python.
• BioSPICE Dashboard — Large collection of tools, integrated via a "Dashboard." Free download (BSD), various platforms.
• CLEML — Carbon Labeling Experiment Markup Language. The libCLEML is freely downloadable (GPL). (Linux/Win).
• CL-SBML — Common Lisp implementation of the SBML Standard (Level 2). I/O library for SBML in Common Lisp.
• COPASI — COPASI is a software application for simulation and analysis of biochemical networks and their dynamics. COPASI is a stand-alone program that supports models in the SBML standard and can simulate their behavior using ODEs or Gillespie's stochastic simulation algorithm; arbitrary discrete events can be included in such simulations. COPASI provides an C++ API with language bindings for Perl, python, R, Java, and Octave and is able to communicate with the Systems Biology Workbench COPASI carries out several analyses of the network and its dynamics and has extensive support for parameter estimation and optimization. COPASI provides means to visualize data in customizable plots, histograms and animations of network diagrams. Please see the COPASI detailed description for a complete list of features. (You can view the test results for this system in the SBML Test Suite Database.)
• JSBML — open-source, Java library for reading, writing, and manipulating SBML files
• 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 supports model archive formats SBML (import and export) and CellML (import only).
• libAnnotationSBML — Java library for reading and writing MIRIAM-compliant SBML annotations
• libSBML — Library for C, C++, .NET, Java, Lisp, Python, Perl, Matlab, Octave, and Ruby. Free Download (LGPL). (Linux/Mac/Win).
• libStruct — The structural analysis library is a C/C++ portable software library for analyzing the structural properties of stoichiometric networks. The library supports the analysis of both flux balance and moiety conservation. The library will accept models in the form of either standard SBML or raw stoichiometry matrices. The software is distributed under the BSD license and was developed through funding from NIH grant 1R01GM081070-01.
• Metannogen — Metannogen is used to browse and annotate existing biological networks given in SBML. It can work together with any network editor that creates SBML files. Its capability of communication with other programs via network sockets allows embedding as a module within other software. It can also be used for network reconstruction to create a network from scratch.
• Odefy — Odefy is a MATLAB and Octave compatible toolbox which a modeling technique called HillCube, a canonical method to convert boolean models into continuous ordinary differential equation (ODE) systems. HillCubes are based on multivariate polynomial interpolation and incorporate Hill kinetics which are known to provide a good approximation of the synergistic dynamics of gene regulation.
• PySCeS — PySCeS: the Python Simulator for Cellular Systems is an extendable toolkit for the analysis and investigation of cellular systems. PySCeS is developed in Python and has been designed to be used both interactively or as a library. It utilises a human readable, model description language for describing models as well as being SBML compatible. PySCeS includes stoichiometric, simulation, steady state and Eigen analysis using direct non-linear root finders. It also includes full support for Metabolic Control Analysis (MCA), the characterisation of static bifurcations, multidimensional parameter scanning and 2/3D graph capabilities. Currently an extension PySCeS-CBM is being developed that allows for the interactive manipulation, modelling and optimization of genome scale, constraint based models (e.g. flux balance analysis)
• SBML Layout — SBML Layout encompasses: 1. a online application for layouting / rendering an SBML file , 2. a library for reading / writing SBML Layout and Rendering information as well as SBGN-ML and 3. a standalone application for displaying files with the SBML Layout or Rendering information. It is written in .net and available under the BSD for all 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)
• semanticSBML — Create, check, visualize, retrieve, cluster, annotate, merge SBML models. The program includes a web based graphical user interface. For tool developers a programming interface (Python) and RESTful web-services are provided. It features advanced functions to edit MIRIAM and SBO terms. The latest version of semanticSBML is fully web based and can be accessed under http://semanticsbml.org/semanticSBML/simple/index
• SimBiology — SimBiology ® is a MATLAB ® product from MathWorks that provides graphical and programmatic tools for computational systems biology and pharmacokinetics. It contains functionality for creating, simulating, and analyzing biological models. The SimBiology desktop lets you build a model using a block diagram editor, a model wizard, or a tabular interface. You can also create a model at the command line or directly from SBML files. SimBiology lets you simulate a model using stochastic or deterministic solvers. The product supports parameter estimation, sensitivity analysis, parameter scans, and other model analysis methods. All SimBiology features can be used together with the MATLAB programming language, letting you customize models, create or modify analysis tasks, and automate your workflow.
• Simulation Core Library — Simulation Core Library is a fast, accurate, and easily usable program for dynamic simulation of models encoded in the Systems Biology Markup Language (SBML). In order to ensure a high reliability of this software, it has been benchmarked against the entire SBML Test Suite (all levels and versions) and all models from the Biomodels.net database. Simulation Core Library is included into SBMLsimulator, which includes a large collection of nature-inspired heuristic optimization procedures for efficient model calibration and provides an intuitive Graphical User Interface (GUI). Simulation Core Library runs on all platforms that provide a standard Java Virtual Machine and is based on the open-source library JSBML. (You can view the test results for this system in the SBML Test Suite Database.)
• SOSlib — SOSlib is both a programming library and a command-line application for symbolic and numerical analysis of a system of ordinary differential equations (ODEs) derived from a chemical reaction network encoded in the Systems Biology Markup Language (SBML). It is written in ANSI/ISO C and distributed under the terms of the GNU Lesser General Public License (LGPL). The package employs libSBML's AST (Abstract Syntax Tree) for formula representation to construct ODE systems, their Jacobian matrix and other derivatives. CVODES, the sensitivity-enabled ODE solver in the SUNDIALS package is used for numerical integration and sensitivity analysis of stiff and non-stiff ODE systems. The native API provides fine-grained interfaces to all internal data structures, symbolic operations and numerical routines, enabling the construction of powerful and efficient analytic applications, hybrid solvers or multi-scale models with interfaces to non SBML data sources. Optional modules based on Graphviz and XMGrace allow a quick inspection of a model's structure and dynamics.
• StochPy — StochPy (Stochastic modelling in Python) is an easy-to-use package, which provides several stochastic simulation algorithms (SSAs), which can be used to simulate biochemical systems in a stochastic manner. Further, several unique and easy-to-use analysis techniques are provided by StochPy including the determination of waiting times, In addition, StochPy can be used as a plug-in into the Python Simulator for Cellular Systems (PySCeS) and can import SBML models descriptions using libSBML allowing it to be tested using the Discrete Stochastic Models Test Suite.
• TERANODE Suite — Suite of tools for model management, design, and simulation. (Linux/Mac/Windows) Commercial (30-day trial available).
• TinkerCell — TinkerCell is a drawing tool for synthetic biology that supports modular models and is highly extensible. One of the extensions is the COPASI C++ library, which adds most of the analysis capabilities from COPASI. Another extension support SBML import/export as well as the Antimony model definition language. TinkerCell supports over 200 Python and Octave functions, allowing users to add plug-ins written in Python or Octave. Users can also upload their plug-in to a central repository (hosted at Sourceforce); all other TinkerCell users will automatically get this plug-in in TinkerCell in the form of a new button. Hierarchical modeling is another key feature in TinkerCell, which is used in conjunction with a custom ontology for automatically generating one or more models from conceptual diagrams.

• BioPARKIN — Robust and reliable parameter identification (e.g. rate constants) in biology-related systems described by (sets of) ODEs or DAEs from given measurements, based on an affine covariant Gauss-Newton algorithm. Additionally, providing a sensible, parameter depending sensitivity analysis for the ODE/DAE systems.
• GINsim — GINsim is dedicated to the logical modelling of regulatory and signalling networks. It allows model definition and provides numerous functionalities for model analyses, including import and export facilities.

• BASIS — BASIS is a project developing web-based services for quantitative study of the biology of ageing. The project also hosts the Stochastic Test Suite.
• BiGG — Database of human, yeast and bacterial metabolites, pathways and reactions as well as SBML reconstructions for metabolic modeling.
• 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
• BioGRID — BioGRID is an online interaction repository with data compiled through comprehensive curation efforts.
• BioModels Database — BioModels Database is a repository of peer-reviewed, published, computational models. These mathematical models are primarily from the field of systems biology, but more generally are those of biological interest. This resource allows biologists to store, search and retrieve published mathematical models. In addition, models in the database can be used to generate sub-models, can be simulated online, and can be converted between different representational formats. This resource also features programmatic access via Web Services.
• BioModels Importer — The database component of BioModels.net is especially designed for working with annotated computational models: each model is carefully reviewed and augmented by human annotators on the BioModels.net team to add metadata linking the model elements to other biological databases and resources. The BioModels Database at the EBI system goes far beyond other collections of models by being a true database, featuring browsing, cross-referencing, searching, and facilities for visualization, exporting models in different formats, and remote API access. The BioModels Importer is such a tool, allowing to search for a specific model (or to quickly access them all). Integrated with SBW the Importer sends a model to JDesigner, Jarnac or any other tool in a snap.
• BRENDA — the BRaunschweig ENzyme Database is a comprehensive information system covering enzymes and their activities. The majority of the data are manually extracted from the primary literature. The content covers information on function, structure, occurrence, preparation and application of enzymes as well as properties of mutants and engineered variants. In 2011, BRENDA introduced the ability to output data in SBML format.
• 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. Furtermore, a webserver has been developed to manage the models, calculations and results easily.
• CADLIVE — CADLIVE (Computer-Aided Design of LIVing systEms) is a comprehensive computational tool for constructing large-scale biological network maps, analyzing the topological features of them, and simulating their dynamics. Using CADLIVE, we rationally design a biological system at the molecular interaction level for an engineering purpose.
• ConsensusPathDB — integrates functional interaction networks including complex protein-protein, metabolic, signaling and gene regulatory interaction networks
• CRdata — CRdata.org offers menu-driven access to the Amazon Elastic Computing Cloud (EC2) and related resources for bioinformatic computing with R and Bioconductor. Users can launch their own processing nodes, and share nodes, scripts, and data with others if they wish.
• 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.
• insilicoIDE — insilicoIDE (ISIDE) assists users to build models of physiological functions with multilevel hierarchical structure and to run simulations. A model is built as a functional network of "modules" which represent physiological entities. In each module, equations such as ODEs and PDEs, parameters and morphological information can be defined. Besides, a module can include a model written in SBML. The SBML model is functionally embedded in the module network. There is an open model database at www.physiome.jp. Users can use models in the database freely as parts to build their own model. The modularity of the model representation in ISIDE makes reuse and integration of multiple models easier. The simulator included in ISIDE supports parallel computing.
• 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 supports model archive formats SBML (import and export) and CellML (import only).
• JWS Online — Online database and simulator.
• Kineticon — Online resource for kinetic data, reactions, enzymes, pathways. SBML L2V1 Export.
• MEMOSys — MEMOSys is a versatile platform for the management, storage, and development of genome-scale metabolic models. It supports the development of new models by providing a built-in version control system which offers access to the complete developmental history. Moreover, the integrated web board, the authorization system, and the definition of user roles allow collaborations across departments and institutions. Research on existing models is facilitated by a search system, references to external databases, and a feature-rich comparison mechanism. MEMOSys provides customizable data exchange mechanisms using the SBML format to enable analysis in external tools. It currently contains 9 annotated microbial metabolic models.
• Meta-All — Pathway database manager.
• MetaCrop — MetaCrop is a database that contains manually curated, highly detailed information about metabolic pathways in crop plants, including location information, transport processes, and reaction kinetics. The web interface supports an easy exploration of the information from overview pathways to single reactions and therefore helps users understanding the metabolism of crop plants. It also allows automatic data export for the creation of detailed models of metabolic pathways to support simulation approaches.
• MetExplore — A web server to link metabolic experiments and genome-scale metabolic networks. MetExplore contains original network filters, allows to export in SBML and visualise filtered metabolic networks, and map masses from metabolic experiments onto complete metabolic networks. It also contains some graph-based methods to enrich the analyses.
• NetPath — 'NetPath' is a curated resource of signal transduction pathways in humans. All pathways are freely available in BioPAX, PSI-MI and SBML formats. The pathways are freely available under an adaptive Creative Commons License which stipulates that the pathways may be used if adequate credit is given to the authors. Feedback on the NetPath website and its contents can be sent to info@netpath.org.
• NetPro — Molecular interaction database (commercial).
• PANTHER Pathway — Pathway database (online resource).
• PathArt — Pathway database collection. (Commercial)
• PAYAO — PAYAO is a community collaborative web service platform for gene-regulatory and biochemical pathway model curation.
• PK-Sim / MoBi — Systems biology software platform for multiscale physiological modeling and simulation with a focus on physiologically-based pharmokinetics and -dynamics (PBPK/PD) including interfaces to MATLAB and R. Available to academic researchers via a free non-commercial license.
• ProcessDB — ProcessDB helps molecular cell biologists manage and test their increasingly complex mechanistic hypotheses. ProcessDB does this with a bio-savvy graphical user interface that helps users formulate, visualize, compare, modify, manage and test their own mechanistic theories of cellular function. All models in ProcessDB can be automatically combined with user-specified experimental protocols and exported to the Berkeley Madonna solver for testing against experimental data. ProcessDB allows investigators to know with precision what their theories predict, and speeds discovery of mechanisms that account for all of the available data.
• Reactome — Pathway database (online resource).
• SABIO-RK — SABIO-RK is a curated database for biochemical reaction kinetics data. The data is drawn from different sources: by extraction from published literature or direct submission by experimenters, and is supplemented with additional data from other databases. The system offers standardized data by the use of controlled vocabularies and annotations pointing to other resources and biological ontologies. It can be accessed either manually via a web-based search interface or automatically via web services that allow direct data access by other tools. Both interfaces support the export of the data together with its annotations in SBML. SABIO-RK facilitates the exchange of kinetic data between experimentalists and modellers, and thereby supports the setup of quantitative computer models.
• SBMLEditor — SBMLeditor a very simple, low level editor of SBML files. Users can create and remove all the necessary bits and pieces of SBML in a controlled way, that maintains the validity and consistency of the final SBML file
• SGMP — The UCSD Signaling Gateway Molecule Pages provide essential information on over 4000 proteins involved in cellular signaling. Each Molecule Page contains regularly updated information derived from public data sources as well as sequence analysis, references and links to other databases. Published Molecule Pages contain an expert-authored review article that describes the biological activity, regulation and localization of the protein. This review is supplemented by highly structured data that illustrate protein-protein interactions, post-translational modifications, subcellular localization and biological function. Prior to publication, there is rigorous peer and editorial review of each Molecule Page. The published pages are citable by digital object identifiers (DOIs). All data in the Molecule Pages are freely available to the public.
• Sigmoid* — Model database, explorer, visualization, Cellerator-based simulations as a web service.
• SignaLink — SignaLink is a multi-layered (onion-like) database made up of signaling pathways, their pathway regulators (e.g., scaffold and endocytotic proteins) and modifier enzymes (e.g., phosphatases, ubiquitin ligases), as well as transcriptional and post-transcriptional regulators of all of these components. The user-friendly website allows the interactive exploration of how each signaling protein is regulated. The customizable download page enables the analysis of any user-specified part of the signaling network of human and two invertebrate model organisms, C. elegans and D. melanogaster.
• SPDBS — SBML-Based Biochemical Pathway Database System
• SYCAMORE — SYCAMORE is a system that provides you with a faciliated access to a number of tools and methods in order to build models of biochemical systems, view, analyse and refine them, as well as perform quick simulations.
• The Cell Collective — The Cell Collective allows laboratory scientists working in different areas of the cell to collectively integrate their knowledge and create large-scale (rule-based) computational models of biological/biochemical networks in a non-technical fashion. Models created in the Cell Collective can be published and made available to the whole community, or shared with a selected group of collaborators, or completely kept private. The software provides an environment not only for the construction and sharing of computational (rule-based) models, but also for real-time, interactive simulations, as well as automated experiments consisting of hundreds of simulations.
• TinkerCell — TinkerCell is a drawing tool for synthetic biology that supports modular models and is highly extensible. One of the extensions is the COPASI C++ library, which adds most of the analysis capabilities from COPASI. Another extension support SBML import/export as well as the Antimony model definition language. TinkerCell supports over 200 Python and Octave functions, allowing users to add plug-ins written in Python or Octave. Users can also upload their plug-in to a central repository (hosted at Sourceforce); all other TinkerCell users will automatically get this plug-in in TinkerCell in the form of a new button. Hierarchical modeling is another key feature in TinkerCell, which is used in conjunction with a custom ontology for automatically generating one or more models from conceptual diagrams.

• acslXtreme — commercial modeling environment that uses a script language called CSL. Has SBML import. Windows only.
• AMIGO — AMIGO means Advanced Model Identification using Global Optimization. AMIGO is a multi-platform (Windows and Linux) matlab-bsed toolbox which covers all the steps of system identification in systems biology. This includes: local and global sensitivity analysis, local and global ranking of parameters, parameter estimation, identifiability analysis and optimal experimental design.
• APMonitor — The APMonitor Modeling Language is optimization software for differential and algebraic equations. It is coupled with large-scale nonlinear programming solvers for data reconciliation, real-time optimization, dynamic simulation, and nonlinear predictive control. It is available as a free web service through MATLAB or Python.
• 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)
• BoolNet — An R package for the generation, reconstruction, simulation and analysis of synchronous, asynchronous, and probabilistic Boolean networks
• BSTLab — GMA and S-Systems based toolbox for Biochemical Systems Theory.
• CADLIVE — CADLIVE (Computer-Aided Design of LIVing systEms) is a comprehensive computational tool for constructing large-scale biological network maps, analyzing the topological features of them, and simulating their dynamics. Using CADLIVE, we rationally design a biological system at the molecular interaction level for an engineering purpose.
• CellNetAnalyzer — CellNetAnalyzer (CNA) is a package for MATLAB and provides a comprehensive and user-friendly environment for structural and functional analysis of biochemical networks. CNA facilitates the analysis of metabolic (stoichiometric) as well as signaling and regulatory networks solely on their network topology, i.e. independent of kinetic mechanisms and parameters. CNA provides a powerful collection of tools and algorithms for structural network analysis which can be started in a menu-controlled manner within interactive network maps. Recently, API functionalities have been added to enable interested users to call algorithms of CNA from external programs. Applications of CNA can be found in systems biology, biotechnology, metabolic engineering, pharmacology, microbiology, chemical engineering.
• COBRA — 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 — COPASI is a software application for simulation and analysis of biochemical networks and their dynamics. COPASI is a stand-alone program that supports models in the SBML standard and can simulate their behavior using ODEs or Gillespie's stochastic simulation algorithm; arbitrary discrete events can be included in such simulations. COPASI provides an C++ API with language bindings for Perl, python, R, Java, and Octave and is able to communicate with the Systems Biology Workbench COPASI carries out several analyses of the network and its dynamics and has extensive support for parameter estimation and optimization. COPASI provides means to visualize data in customizable plots, histograms and animations of network diagrams. Please see the COPASI detailed description for a complete list of features. (You can view the test results for this system in the SBML Test Suite Database.)
• DOTcvpSB — MatLab toolbox for optimization of models.
• GNAT — GNAT is an open source MATLAB-based toolbox. It provides functions for reading, writing, manipulation, visualization and simulation of glycan structures and glycosylation reaction networks. It is written in MATLAB and Java. It is thus platform-independent. It has been tested in Windows (Windows 7), Linux (Ubuntu), and Mac OS (X Lion) platforms.
• 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 supports model archive formats SBML (import and export) and CellML (import only).
• MatCont — MatCont is a Matlab software package for the numerical study of parameterized continuous and discrete dynamical systems.
• MathSBML — SBML import/export and simulation within Mathematica.
• Metatool — A tool for metabolic pathway analysis with the main focus in elementary modes calculation. Enzyme subsets and conservation relations are also determined.
• Odefy — Odefy is a MATLAB and Octave compatible toolbox which a modeling technique called HillCube, a canonical method to convert boolean models into continuous ordinary differential equation (ODE) systems. HillCubes are based on multivariate polynomial interpolation and incorporate Hill kinetics which are known to provide a good approximation of the synergistic dynamics of gene regulation.
• PK-Sim / MoBi — Systems biology software platform for multiscale physiological modeling and simulation with a focus on physiologically-based pharmokinetics and -dynamics (PBPK/PD) including interfaces to MATLAB and R. Available to academic researchers via a free non-commercial license.
• PottersWheel — ODE based Simulation, model fitting, visualization, clustering, model design. (Free download; Optimization toolbox recommended).
• PySCeS — PySCeS: the Python Simulator for Cellular Systems is an extendable toolkit for the analysis and investigation of cellular systems. PySCeS is developed in Python and has been designed to be used both interactively or as a library. It utilises a human readable, model description language for describing models as well as being SBML compatible. PySCeS includes stoichiometric, simulation, steady state and Eigen analysis using direct non-linear root finders. It also includes full support for Metabolic Control Analysis (MCA), the characterisation of static bifurcations, multidimensional parameter scanning and 2/3D graph capabilities. Currently an extension PySCeS-CBM is being developed that allows for the interactive manipulation, modelling and optimization of genome scale, constraint based models (e.g. flux balance analysis)
• RANGE — Random network generator. Noise added by R-script. Source code in C, yacc, lex. (GPL).
• RMBNToolbox — Toolbox for generating random notebooks (GPL).
• RSBML — SBML interface library for R (GPL). (available from CRAN).
• SBMLR — This package uses the R package XML to bring SBML models into and out of R.
• SBMLToolbox — Manipulation of SBML in both the MATLAB and Octave environments. Some simulation support but the main focus is on allowing users to adapt SBML to their existing MATLAB/Octave functions. (You can view the test results for this system in the SBML Test Suite Database.)
• 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).
• 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)
• SimBiology — SimBiology ® is a MATLAB ® product from MathWorks that provides graphical and programmatic tools for computational systems biology and pharmacokinetics. It contains functionality for creating, simulating, and analyzing biological models. The SimBiology desktop lets you build a model using a block diagram editor, a model wizard, or a tabular interface. You can also create a model at the command line or directly from SBML files. SimBiology lets you simulate a model using stochastic or deterministic solvers. The product supports parameter estimation, sensitivity analysis, parameter scans, and other model analysis methods. All SimBiology features can be used together with the MATLAB programming language, letting you customize models, create or modify analysis tasks, and automate your workflow.
• Simpathica — ODE based simulation. Part of BioSpice.
• SloppyCell — SloppyCell is focused on parameter estimation and sensitivity analysis for ODE models. In particular, SloppyCell includes semi-analytic sensitivity integration, along with capability for building Bayesian ensembles of parameters sets consistent with given data.
• SYCAMORE — SYCAMORE is a system that provides you with a faciliated access to a number of tools and methods in order to build models of biochemical systems, view, analyse and refine them, as well as perform quick simulations.
• 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.
• Wolfram SystemModeler — Wolfram SystemModeler is a high-fidelity modeling software based on the Modelica language. It allows for hierarchical, multidomain, and hybrid systems modeling using a graphical drag and drop environment, and/or an equation based textual interface. And it integrates with the Wolfram technology platform to enable modeling, simulation, and analysis (of many types), all together achieving an agile design optimization loop. Provided with SystemModeler is a large set of built-in model libraries, including the BioChem library - an SBML compatible Modelica library designed for biochemical systems. By making use of the BioChem library, SystemModeler lets you build, simulate, and visualize PKPD and systems biology models. The software also provides SBML import and export functionality to allow Modelica-SBML model exchange.
• xCellerator — Mathematica based ODE simulator. SBML inport/export uses MathSBML. Requires Mathematica. Free download (LGPL). (Linux/Mac/Win).

• AMIGO — AMIGO means Advanced Model Identification using Global Optimization. AMIGO is a multi-platform (Windows and Linux) matlab-bsed toolbox which covers all the steps of system identification in systems biology. This includes: local and global sensitivity analysis, local and global ranking of parameters, parameter estimation, identifiability analysis and optimal experimental design.
• APMonitor — The APMonitor Modeling Language is optimization software for differential and algebraic equations. It is coupled with large-scale nonlinear programming solvers for data reconciliation, real-time optimization, dynamic simulation, and nonlinear predictive control. It is available as a free web service through MATLAB or Python.
• 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.
• 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 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)
• BioPARKIN — Robust and reliable parameter identification (e.g. rate constants) in biology-related systems described by (sets of) ODEs or DAEs from given measurements, based on an affine covariant Gauss-Newton algorithm. Additionally, providing a sensible, parameter depending sensitivity analysis for the ODE/DAE systems.
• 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.
• BioSyS — a system that facilitates the study of biological systems that are described by Ordinary Differential Equations (ODEs). This software is designed to be capable of performing distributed simulations using Grid computing, stores the results in a database and allow further studies, incorporating various types of analysis such as charts, population dynamics, algorithms of clustering, classification, user-defined rules, stability and bifurcations, using data mining techniques. BioSyS 1.0 makes it easier for researchers with a number of tools and algorithms that allow them to carry out investigations in an easier way.
• BioTapestry — Graphical model development and simulation tool for genetic regulatory networks based on JRE. Uses Java Web Start. Free download. SBML export.
• BoolNet — An R package for the generation, reconstruction, simulation and analysis of synchronous, asynchronous, and probabilistic Boolean networks
• 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. Furtermore, a webserver has been developed to manage the models, calculations and results easily.
• CADLIVE — CADLIVE (Computer-Aided Design of LIVing systEms) is a comprehensive computational tool for constructing large-scale biological network maps, analyzing the topological features of them, and simulating their dynamics. Using CADLIVE, we rationally design a biological system at the molecular interaction level for an engineering purpose.
• 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.
• Cell Illustrator — Graphical model editor; Petri-net based simulation algorithm; SBML Import. Commercial. (Linux/Mac/Win).
• CellDesigner — CellDesigner is a structured diagram editor for drawing gene-regulatory and biochemical networks. Networks are drawn based on the process diagram, with graphical notation system. CellDesigner supports simulation and parameter scan by an integration with SBML ODE Solver and Copasi. By using CellDesigner, users can browse and modify existing SBML models with references to existing databases (MIRIAM supported), simulate and view the dynamics through an intuitive graphical interface.
• CellNetAnalyzer — CellNetAnalyzer (CNA) is a package for MATLAB and provides a comprehensive and user-friendly environment for structural and functional analysis of biochemical networks. CNA facilitates the analysis of metabolic (stoichiometric) as well as signaling and regulatory networks solely on their network topology, i.e. independent of kinetic mechanisms and parameters. CNA provides a powerful collection of tools and algorithms for structural network analysis which can be started in a menu-controlled manner within interactive network maps. Recently, API functionalities have been added to enable interested users to call algorithms of CNA from external programs. Applications of CNA can be found in systems biology, biotechnology, metabolic engineering, pharmacology, microbiology, chemical engineering.
• Cellware — Block diagram model editor & simulator. SBML import. Free download (Academic/Non-Profit) (Linux/Mac/Win).
• CompuCell3D — CompuCell3D (CC3D) is an open-source environment for building and running multi-cell, multi-scale simulations based on the GGH model, utilizing the Systems Biology Workbench (SBW) suite. Scripting use the CC3DML Model Description Language and Python. Can simulate at more than 5 x 10^5 cells / processor; provides PDE support; utilizes SOSLIB/Jarnac/JDesigner.
• COPASI — COPASI is a software application for simulation and analysis of biochemical networks and their dynamics. COPASI is a stand-alone program that supports models in the SBML standard and can simulate their behavior using ODEs or Gillespie's stochastic simulation algorithm; arbitrary discrete events can be included in such simulations. COPASI provides an C++ API with language bindings for Perl, python, R, Java, and Octave and is able to communicate with the Systems Biology Workbench COPASI carries out several analyses of the network and its dynamics and has extensive support for parameter estimation and optimization. COPASI provides means to visualize data in customizable plots, histograms and animations of network diagrams. Please see the COPASI detailed description for a complete list of features. (You can view the test results for this system in the SBML Test Suite Database.)
• CRdata — CRdata.org offers menu-driven access to the Amazon Elastic Computing Cloud (EC2) and related resources for bioinformatic computing with R and Bioconductor. Users can launch their own processing nodes, and share nodes, scripts, and data with others if they wish.
• Cyto-Sim — Stochastic simulator based on automata theory (P system). Free download. JVM Based.
• DBSolve — DBSolveOptimum is a free software for kinetic modeling of metabolic pathways, analysis, and fitting parameters to experimental data. The program has text-based user interface for model description and graphical interface for data analysis. In addition to standart algorithms of simulation (ODE solver, explicit solver, steady-state analysis) the software include also automated local sencetivity analysis, parameters optimization procedures and bifurcaion analysis. The last version of DBSolveOptimum includes advanced tool for data visualization.
• 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).
• 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.
• 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.
• Facile — Facile / EasyStoch. A command-line network compiler for systems biology. Facile reads models given in a simple and human-readable textual input format and exports the model in a format for readable by Matlab, Mathematica, Maple, XPP/AUTO. Other tools are supported via SBML export. For stochastic simulations, Facile uses the EasyStoch stochastic simulator. An important feature of EasyStoch that distinguishes it from other Gillespie-algorithm implementations is that it is capable of simulating dynamically changing or noisy biochemical parameters (i.e. extrinsic noise).
• FASIMU — FASIMU is a command line oriented software implementing the most frequently applied FBA algorithms. It offers the first freely available implementation of (i) weighted flux minimization, (ii) fitness maximization for partially inhibited enzymes, and (iii) the concentration-based thermodynamic feasibility constraint. It allows heterogenous computation series suited for network pruning, leak analysis, FVA, and systematic probing of metabolic objectives for network curation controlled by an intuitive description file. The metabolic network can be supplied in SBML, CellNetAnalyzer, and plain text format. FASIMU uses the optimization capabilities of free (lp solve and GLPK) and commercial solvers (CPLEX, LINDO). The results can be visualized in Cytoscape or BiNA using newly developed plugins. The platform-independent program is an open-source project, freely available under GNU public license, including manual, tutorial, BiNA and Cytoscape plugin and respective manuals.
• 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.
• Genetdes — Network optimization using Simulated Annealing. SBML Import/Export. Free download, requires email license (CCL- AN). (Linux)
• Genetic Network Analyzer — Genetic Network Analyzer (GNA) is a computer tool for the modeling, simulation, analysis and verification of genetic regulatory networks. The aim of GNA is to assist biologists and bioinformaticians in constructing a qualitative model of a genetic regulatory network from knowledge about regulatory interactions and gene expression data. GNA provides a variety of functions to analyze the steady-state and transient dynamics of the network, among other things by exploiting state-of-the-art model-checking tools.
• Gepasi — Forerunner of COPASI. ODE simulations, metabolic analysis. SBML L1 Inport/Export. (Windows or Linux under Wine). Limited license.
• Gillespie2 — from the BASIS Project. Source code.
• GINsim — GINsim is dedicated to the logical modelling of regulatory and signalling networks. It allows model definition and provides numerous functionalities for model analyses, including import and export facilities.
• GNAT — GNAT is an open source MATLAB-based toolbox. It provides functions for reading, writing, manipulation, visualization and simulation of glycan structures and glycosylation reaction networks. It is written in MATLAB and Java. It is thus platform-independent. It has been tested in Windows (Windows 7), Linux (Ubuntu), and Mac OS (X Lion) platforms.
• GNU MCSim — GNU MCSim is a free standalone simulation package that allows you to design your own statistical or simulation models. It efficiently performs Bayesian inference through Markov Chain Monte Carlo simulations. Standard Monte Carlo and experimental design optimization are also available. GNU MCSim can import and simulate levels 1 and 2 SBML models
• iBioSim — The iBioSim tool supports the modeling, analysis, and design of genetic circuits with applications in both systems and synthetic biology. It includes editors to construct genetic circuit models (GCM), Systems Biology Markup Language (SBML) models (L2V4 and L3V1 supported), and labeled Petri net (LPN) models. Models can be constructed by hand, imported from model databases, or learned from experimental data. These models can be analyzed using a variety of ODE and stochastic simulators as well as Markov chain analysis. The efficiency of these analysis methods is enhanced using a variety of automatic reaction-based and logical abstractions. The analysis results can be plotted as graphs or visualized upon the genetic circuit schematic. (You can view the test results for this system in the SBML Test Suite Database.)
• insilicoIDE — insilicoIDE (ISIDE) assists users to build models of physiological functions with multilevel hierarchical structure and to run simulations. A model is built as a functional network of "modules" which represent physiological entities. In each module, equations such as ODEs and PDEs, parameters and morphological information can be defined. Besides, a module can include a model written in SBML. The SBML model is functionally embedded in the module network. There is an open model database at www.physiome.jp. Users can use models in the database freely as parts to build their own model. The modularity of the model representation in ISIDE makes reuse and integration of multiple models easier. The simulator included in ISIDE supports parallel computing.
• Jarnac — SBW tool for metabolic analysis, includes dynamic simulation. Simulation engine for JDesigner. BSD License.
• JigCell — JigCell is a set of computational tools with user-friendly interfaces developed for studying complex biochemical regulatory systems in general and the cell cycle control system in particular. For example, The JigCell Model Builder (JCMB) aides the modeler in defining a system to be modeled using SBML with a novel spreadsheet interface, allowing a large amount of data to be displayed in an organized manner. The JigCell Run Manager (JCRM) allows a user to specify a set of specifications for simulation runs using a spreadsheet interface. JigCell Aggregation Connector has been designed to define models in terms of components, for the purpose of being combined in a larger model. JigCell also aims in parameter estimation. A parameter estimator (PET, Parameter Estimation Toolkit) takes a biological model, experimental data, and the relationship between the model and data. Using this information the parameter estimator uses numerical tools to vary the parameters to the model looking for the parameters that best fit the experimental data.
• 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 supports model archive formats SBML (import and export) and CellML (import only).
• Kinsolver — A simulator for biochemical and gene regulatory networks
• libSBMLSim — LibSBMLSim is a library for simulating an SBML model which contains Ordinary Differential Equations (ODEs). LibSBMLSim provides simple command-line tool and several APIs to load an SBML model, perform numerical integration (simulate) and export its results. Both explicit and implicit methods are supported on libSBMLSim. (You can view the test results for this system in the SBML Test Suite Database.)
• MatCont — MatCont is a Matlab software package for the numerical study of parameterized continuous and discrete dynamical systems.
• MesoRD — MesoRD is a stochastic and deterministic simulator of coupled chemical reactions and diffusions in space.
• Metaboflux — Metaboflux is a computational tool for predicting flux distribution in metabolic networks under multiple and various constraints deducted from the experiments. It aims to increase the biological relevance of models by integrating experimental data. The tool is available in two versions : a command line tool optimized for running on HPC servers and a user-friendly interface designed to define model parameters and run simple computations. Metaboflux embedded a stochastic simulator of metabolic networks coupled with a non linear solver (GSL). It solves constraints defined as proportions (for example, metabolite proportions) or as equations. Results can be visualized directly in Metaboflux or within specific tools like Systrip.
• MetaFluxNet — MetaFluxNet is a program package for managing information on the metabolic reaction network and for quantitatively analyzing metabolic fluxes in an interactive and customized way, which allows users to interpret and examine metabolic behavior in response to genetic and/or environmental modifications. As a result, quantitative in silico simulations of metabolic pathways can be carried out to understand the metabolic status and to design the metabolic engineering strategies.
• 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 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 NeuroML.
• Narrator — Graphical model design and simulation. Java-based, platform independent. Open source/free download (LGPL).
• nemo — RANGE will generate large random transcription networks, with up to 16,000 genes, in the NEMO language. NEMO's compiler (nemo2sbml) uses lex and yacc to output a Systems Biology Markup Language (SBML) model for either user-specified and/or randomized gene input functions. The SBML model of the known network may be input to a biochemical simulator (i.e. COPASI), allowing the generation of synthetic microarray data for algorithm development purposes. Alternately, NEMO may be used by itself to simply describe and SBML-ize your existing biochemical network.
• NetBuilder' — NetBuilder' is a software tool that is intended to help experimentalists creating and manipulating the mathematical representations they need to predict the behaviour of their systems. NetBuilder' has a graphical user interface, which allows its users to create a picture of the (known) components and interactions in the system, and enter quantitative information, such as know or estimated quantities and rates. A (hidden) translator converts the picture and the other data into a mathematical description, whereupon NetBuilder's "simulation engine" may be used to find out how the modelled system responds to changing input.
• Odefy — Odefy is a MATLAB and Octave compatible toolbox which a modeling technique called HillCube, a canonical method to convert boolean models into continuous ordinary differential equation (ODE) systems. HillCubes are based on multivariate polynomial interpolation and incorporate Hill kinetics which are known to provide a good approximation of the synergistic dynamics of gene regulation.
• optflux — Simulation
• Oscill8 — Bifurcation and Simulation. Windows Binary. (BSD).
• Pathway Solver — ODE based simulation. Commercial. (formerly runSMBL)
• PathwayLab — PathwayLab is a tool for modeling, analysis, and information management of biochemical pathways. It streamlines the pathway building process by a rich and flexible set of graphical building blocks for specifying biochemical entities, reaction, and control mechanisms. The pathway models are built using drag and drop from stencils into a workspace, which makes it very easy to rapidly build models of biochemical reaction networks such as signaling and metabolic pathways as well as gene regulatory networks. PathwayLab depends on Microsoft Visio.
• PET — Parameter optimization and exploration is the primary feature of PET. Some of the other tasks PET can perform are simulations, setting up multiple experiments for a model, comparing parameter sets, and exporting plots for presentations.
• PhysioLab Modeler — Whole organism modeling environment. Commercial.
• PK-Sim / MoBi — Systems biology software platform for multiscale physiological modeling and simulation with a focus on physiologically-based pharmokinetics and -dynamics (PBPK/PD) including interfaces to MATLAB and R. Available to academic researchers via a free non-commercial license.
• PNK — Petri Net Simulator (JRE/SBW required) (GPL).
• ProcessDB — ProcessDB helps molecular cell biologists manage and test their increasingly complex mechanistic hypotheses. ProcessDB does this with a bio-savvy graphical user interface that helps users formulate, visualize, compare, modify, manage and test their own mechanistic theories of cellular function. All models in ProcessDB can be automatically combined with user-specified experimental protocols and exported to the Berkeley Madonna solver for testing against experimental data. ProcessDB allows investigators to know with precision what their theories predict, and speeds discovery of mechanisms that account for all of the available data.
• PyDSTool — PyDSTool is a Python-based Dynamical Systems Toolkit. With PyDSTool we aim to provide a powerful suite of computational tools for the development, simulation, and analysis of dynamical systems that are used for the modeling of physical processes in many scientific disciplines, but especially in the biological sciences. We place emphasis on the support of data analysis and model fitting as a core part of the process of data-driven modeling. Our focus is on models involving ordinary differential equations (ODEs), differential-algebraic equations (DAEs), and discrete maps. Our approach differs from many existing software packages because of our focus on making model building, simulation, and analysis intuitive and efficient for an advanced end-user (who is unlikely to be either a mathematician or a computer programmer by trade) without sacrificing speed. We say for advanced users because PyDSTool does not provide a graphical interface, but instead a scripting environment with flexible, programmable library tools.
• PySCeS — PySCeS: the Python Simulator for Cellular Systems is an extendable toolkit for the analysis and investigation of cellular systems. PySCeS is developed in Python and has been designed to be used both interactively or as a library. It utilises a human readable, model description language for describing models as well as being SBML compatible. PySCeS includes stoichiometric, simulation, steady state and Eigen analysis using direct non-linear root finders. It also includes full support for Metabolic Control Analysis (MCA), the characterisation of static bifurcations, multidimensional parameter scanning and 2/3D graph capabilities. Currently an extension PySCeS-CBM is being developed that allows for the interactive manipulation, modelling and optimization of genome scale, constraint based models (e.g. flux balance analysis)
• roadRunner — roadRunner is a high performance simulator for cellular networks. roadRunner accepts standard SBML (Levels 1-3) 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. (You can view the test results for this system in the SBML Test Suite Database.)
• SBML2NEURON — SBML2NEURON is a provisional implementation of an SBML to NEURON converter. This uses the Python bindings of libSBML to generate an NMODL file containing the model represented in a basic SBML file, which can then be inserted onto a section in NEURON for simulation. Note that only a restricted set of SBML elements are supported (see the notes), but it can be used to simulate some of the models in BioModels Database. This is a work in progress and will be developed further to allow closer integration between NeuroML and SBML in realistic neuronal models.
• SBML-PET-MPI — SBML-PET-MPI is a parallel parameter estimation tool for Systems Biology Markup Language (SBML) based models. The tool allows the user to perform parameter estimation, parameter uncertainty and identifiability analysis by collectively fitting multiple experimental data sets. SBML-PET-MPI can run on Windows, Linux and Mac OS X systems.
• SBMLR — This package uses the R package XML to bring SBML models into and out of R.
• 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.
• SBMLToolbox — Manipulation of SBML in both the MATLAB and Octave environments. Some simulation support but the main focus is on allowing users to adapt SBML to their existing MATLAB/Octave functions. (You can view the test results for this system in the SBML Test Suite Database.)
• 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).
• 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)
• sbw: javasim — Set of Java simulators implementing; Chemical Langevin, CVODE, Gibson NRM, Gillespie DM, Gillespie FRM, and LSODA.
• sbw: stochastic simulator — GillespieGUI is a new user interface for biochemical networks that has been designed to integrate both tasks of interest to biologists - namely, simulating a model and analyzing the data. The data simulation is carried out by a stochastic simulator, whose parameters such as simulation start and end times, as well as data or time sampling options can be set prior to starting the simulation. This being a tool designed for statistical analysis, users can specify the number of runs of the model that the simulation should generate. Once the data for the specified number of runs has been generated, the tool then computes correlations between various species, along with their power spectral densities and transfer functions. In particular the following capabilities are supported:
• SED-ML Web Tools — The SED-ML Web tools represent a suite of tools for creating, editing, simulating and validating SED-ML files.SED-ML descriptions can be created directly by uploading an SBML model.
• SIMBA — Wastewater simulation. SBML Support unspecified. Commercial(?).
• SimBiology — SimBiology ® is a MATLAB ® product from MathWorks that provides graphical and programmatic tools for computational systems biology and pharmacokinetics. It contains functionality for creating, simulating, and analyzing biological models. The SimBiology desktop lets you build a model using a block diagram editor, a model wizard, or a tabular interface. You can also create a model at the command line or directly from SBML files. SimBiology lets you simulate a model using stochastic or deterministic solvers. The product supports parameter estimation, sensitivity analysis, parameter scans, and other model analysis methods. All SimBiology features can be used together with the MATLAB programming language, letting you customize models, create or modify analysis tasks, and automate your workflow.
• Simulation Core Library — Simulation Core Library is a fast, accurate, and easily usable program for dynamic simulation of models encoded in the Systems Biology Markup Language (SBML). In order to ensure a high reliability of this software, it has been benchmarked against the entire SBML Test Suite (all levels and versions) and all models from the Biomodels.net database. Simulation Core Library is included into SBMLsimulator, which includes a large collection of nature-inspired heuristic optimization procedures for efficient model calibration and provides an intuitive Graphical User Interface (GUI). Simulation Core Library runs on all platforms that provide a standard Java Virtual Machine and is based on the open-source library JSBML. (You can view the test results for this system in the SBML Test Suite Database.)
• Simulation Tool — The Simulation Tool is an environment for interactive exploration of SBML Models (L1-L3). It allows for simulation and analysis of models, provided capabilites (through simulators like RoadRunner) to define signals and events to interact with the model. Also features Steady State and Frequency Analysis.
• SloppyCell — SloppyCell is focused on parameter estimation and sensitivity analysis for ODE models. In particular, SloppyCell includes semi-analytic sensitivity integration, along with capability for building Bayesian ensembles of parameters sets consistent with given data.
• SmartCell — Stochastic Reaction/Diffusion Simulator (Linux/Mac/Win) (Acad/NP).
• Snoopy — a software tool to design and animate hierarchical graphs, among others Petri nets. To investigate biomolecular networks, Snoopy provides a unifying Petri net framework comprising a family of related Petri net classes. Models can be hierarchically structured, allowing for the mastering of larger networks. To move easily between the qualitative, stochastic and continuous modelling paradigms, models can be converted into each other. We get models sharing structure, but being specialized by their kinetic information. The analysis and iterative reverse engineering of biomolecular networks is supported by the simultaneous use of several Petri net classes, while the GUI adapts dynamically to the active one. Built-in animation and simulation are complemented by exports to various analysis tools.
• SOSlib — SOSlib is both a programming library and a command-line application for symbolic and numerical analysis of a system of ordinary differential equations (ODEs) derived from a chemical reaction network encoded in the Systems Biology Markup Language (SBML). It is written in ANSI/ISO C and distributed under the terms of the GNU Lesser General Public License (LGPL). The package employs libSBML's AST (Abstract Syntax Tree) for formula representation to construct ODE systems, their Jacobian matrix and other derivatives. CVODES, the sensitivity-enabled ODE solver in the SUNDIALS package is used for numerical integration and sensitivity analysis of stiff and non-stiff ODE systems. The native API provides fine-grained interfaces to all internal data structures, symbolic operations and numerical routines, enabling the construction of powerful and efficient analytic applications, hybrid solvers or multi-scale models with interfaces to non SBML data sources. Optional modules based on Graphviz and XMGrace allow a quick inspection of a model's structure and dynamics.
• STEPS — STEPS is a package for exact stochastic simulation of reaction-diffusion systems in arbitrarily complex 3D geometries. Our core simulation algorithm is an implementation of Gillespie's SSA, extended to deal with diffusion of molecules over the elements of a 3D tetrahedral mesh. Tetrahedral meshes offer much better morphological resolution than the cubic voxels used in other SSA based software and so STEPS is the first spatial SSA software to allow realistic boundary representation. While STEPS was mainly developed for simulating detailed models of neuronal signaling pathways in dendrites and around synapses, it is a general tool and can be used for studying any biochemical pathway in which spatial gradients and morphology are thought to play a role. We have implemented STEPS as a set of Python modules, which means STEPS users can use Python scripts to control all aspects of setting up the model, generating a mesh, controlling the simulation and generating and analyzing output. The core computational routines are still implemented as C/C++ extension modules for maximal speed of execution.
• StochKit — C++ library that provides various SSA, tau-leaping and adaptive step size algorithms. Source code only. (Linux) (Acad/NP).
• StochPy — StochPy (Stochastic modelling in Python) is an easy-to-use package, which provides several stochastic simulation algorithms (SSAs), which can be used to simulate biochemical systems in a stochastic manner. Further, several unique and easy-to-use analysis techniques are provided by StochPy including the determination of waiting times, In addition, StochPy can be used as a plug-in into the Python Simulator for Cellular Systems (PySCeS) and can import SBML models descriptions using libSBML allowing it to be tested using the Discrete Stochastic Models Test Suite.
• StochSim — STOCHSIM is a stochastic simulator for (bio)chemical reactions. The particles are represented as individual software objects which react according to probabilities derived from concentrations and rate constants. In the version 1.4 of STOCHSIM simple two-dimensional spatial structures have been implemented, in which nearest-neighbour interactions of molecules can be simulated.
• STOCKS — SSA, Gibson-Bruck, and Tau-Leaping algorithms. Command line based tool. (source code, Linux/Windows) (GPL).
• SurreyFBA — SurreyFBA provides constraint-based simulations of genome scale metabolic networks in a free, stand-alone software. In addition to basic simulation protocols the tool also implements the analysis of minimal substrate and product sets, which is useful for metabolic engineering and prediction of nutritional requirements in complex in vivo environments. The SurreyFBA is based on a command line interface to the GLPK solver distributed as binary and source code for the three major operating systems. The sfba command line tool, implemented in C++, is easily executed within scripting languages used in the bioinformatics community and provides efficient implementation of tasks requiring iterative calls to the linear programming solver. SurreyFBA includes JyMet, a graphics user interface allowing spreadsheet based model presentation, visualization of numerical results on metabolic networks represented in the Petri net convention, as well as in charts and plots.
• SYCAMORE — SYCAMORE is a system that provides you with a faciliated access to a number of tools and methods in order to build models of biochemical systems, view, analyse and refine them, as well as perform quick simulations.
• 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.
• The Cell Collective — The Cell Collective allows laboratory scientists working in different areas of the cell to collectively integrate their knowledge and create large-scale (rule-based) computational models of biological/biochemical networks in a non-technical fashion. Models created in the Cell Collective can be published and made available to the whole community, or shared with a selected group of collaborators, or completely kept private. The software provides an environment not only for the construction and sharing of computational (rule-based) models, but also for real-time, interactive simulations, as well as automated experiments consisting of hundreds of simulations.
• TinkerCell — TinkerCell is a drawing tool for synthetic biology that supports modular models and is highly extensible. One of the extensions is the COPASI C++ library, which adds most of the analysis capabilities from COPASI. Another extension support SBML import/export as well as the Antimony model definition language. TinkerCell supports over 200 Python and Octave functions, allowing users to add plug-ins written in Python or Octave. Users can also upload their plug-in to a central repository (hosted at Sourceforce); all other TinkerCell users will automatically get this plug-in in TinkerCell in the form of a new button. Hierarchical modeling is another key feature in TinkerCell, which is used in conjunction with a custom ontology for automatically generating one or more models from conceptual diagrams.
• Trelis — Monte Carlo Simulator.
• VANTED — This system makes it possible to load and edit graphs, which may represent biological pathways or functional hierarchies. It is possible to map experimental datasets onto the graph elements and visualize time series data or data of different genotypes or environmental conditions in the context of a the underlying biological processes. Built-in statistic functions allow a fast evaluation of the data (e.g. t-Test or correlation analysis). Vanted can be extended for various functionalities, e.g. flux simulation, database access and 3D visualisation.
• 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). (You can view the test results for this system in the SBML Test Suite Database.)
• WebCell — Online simulator, model builder, metabolic controal analysis. Includes database of bimodels and JWS models. Registration required.
• Wolfram SystemModeler — Wolfram SystemModeler is a high-fidelity modeling software based on the Modelica language. It allows for hierarchical, multidomain, and hybrid systems modeling using a graphical drag and drop environment, and/or an equation based textual interface. And it integrates with the Wolfram technology platform to enable modeling, simulation, and analysis (of many types), all together achieving an agile design optimization loop. Provided with SystemModeler is a large set of built-in model libraries, including the BioChem library - an SBML compatible Modelica library designed for biochemical systems. By making use of the BioChem library, SystemModeler lets you build, simulate, and visualize PKPD and systems biology models. The software also provides SBML import and export functionality to allow Modelica-SBML model exchange.
• 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)

• 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.
• APMonitor — The APMonitor Modeling Language is optimization software for differential and algebraic equations. It is coupled with large-scale nonlinear programming solvers for data reconciliation, real-time optimization, dynamic simulation, and nonlinear predictive control. It is available as a free web service through MATLAB or Python.
• 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.
• BioPAX2SBML — The BioPAX2SBML converter translates BioPAX formats (Level 2 and 3) into SBML format (Level 3 Version 1 with qual) including reactions and relations in one model. Thus, the resulting models can be used for further quantitative and qualitative modeling purposes.
• 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. Furtermore, a webserver has been developed to manage the models, calculations and results easily.
• CADLIVE — CADLIVE (Computer-Aided Design of LIVing systEms) is a comprehensive computational tool for constructing large-scale biological network maps, analyzing the topological features of them, and simulating their dynamics. Using CADLIVE, we rationally design a biological system at the molecular interaction level for an engineering purpose.
• 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).
• CellML2SBML — Converts CELLML to SBML
• CL-SBML — Common Lisp implementation of the SBML Standard (Level 2). I/O library for SBML in Common Lisp.
• COPASI — COPASI is a software application for simulation and analysis of biochemical networks and their dynamics. COPASI is a stand-alone program that supports models in the SBML standard and can simulate their behavior using ODEs or Gillespie's stochastic simulation algorithm; arbitrary discrete events can be included in such simulations. COPASI provides an C++ API with language bindings for Perl, python, R, Java, and Octave and is able to communicate with the Systems Biology Workbench COPASI carries out several analyses of the network and its dynamics and has extensive support for parameter estimation and optimization. COPASI provides means to visualize data in customizable plots, histograms and animations of network diagrams. Please see the COPASI detailed description for a complete list of features. (You can view the test results for this system in the SBML Test Suite Database.)
• ecellJ — Converts between Ecell models and various other formats including SBML and open office spreadsheets.
• Facile — Facile / EasyStoch. A command-line network compiler for systems biology. Facile reads models given in a simple and human-readable textual input format and exports the model in a format for readable by Matlab, Mathematica, Maple, XPP/AUTO. Other tools are supported via SBML export. For stochastic simulations, Facile uses the EasyStoch stochastic simulator. An important feature of EasyStoch that distinguishes it from other Gillespie-algorithm implementations is that it is capable of simulating dynamically changing or noisy biochemical parameters (i.e. extrinsic noise).
• 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.
• 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 supports model archive formats SBML (import and export) and CellML (import only).
• KEGG2SBML — Converts KEGG models to SBML.
• KEGGconverter — KEGGconverter automatically produces merged and converted to SBML fully functional pathway models, enhanced with default kinetics, by inputting only KGML files.The final derived models do not enclose trivial metabolites -reproducing inconsistencies of the KGML visualization-oriented, simplified information pattern- but at the same time they contain all the available information regarding the number of the included reactions in each pathway. Furthermore, additional reactions to neighbouring pathways are constructed which indicate the direction of the metabolic flows in the network and thus providing better stability in the boundary conditions of the models.
• KEGGtranslator — Nowadays, the KEGG PATHWAY database provides a widely used service for pathway-based information. It contains manually drawn pathway maps with information about the genes, reactions and relations contained therein. To store these pathways, KEGG uses an own XML-format (called “KGML”). Parsers and translators are needed to process the pathway maps for usage in other applications and algorithms. We have developed KEGGtranslator, which is an easy-to-use stand-alone application that can visualize and convert KGML formatted XML-files into multiple output formats. Unlike other translators, KEGGtranslator supports a plethora of output formats, is able to augment the information in translated documents (e.g., MIRIAM annotations) beyond the scope of the KGML document, and amends missing components to fragmentary reactions within the pathway to allow simulations on those. KEGGtranslator converts KEGG files (KGML formatted XML-files) to SBML, GML, GraphML, JPG, GIF, LaTeX, etc. KEGG pathways can be obtained from ftp://ftp.genome.jp/pub/kegg/xml/kgml
• MetaFluxNet — MetaFluxNet is a program package for managing information on the metabolic reaction network and for quantitatively analyzing metabolic fluxes in an interactive and customized way, which allows users to interpret and examine metabolic behavior in response to genetic and/or environmental modifications. As a result, quantitative in silico simulations of metabolic pathways can be carried out to understand the metabolic status and to design the metabolic engineering strategies.
• MetExplore — A web server to link metabolic experiments and genome-scale metabolic networks. MetExplore contains original network filters, allows to export in SBML and visualise filtered metabolic networks, and map masses from metabolic experiments onto complete metabolic networks. It also contains some graph-based methods to enrich the analyses.
• MuVal (Multi-valued logic) — MuVal— Multi-valued logic (MuVal) is a free web service that can convert CellNetAnalyzer (CNA) compliant logic models of signalling networks in a way that facilitates handling of combinatorial regulation. Inhibition or activation of reactions by multiple regulators is a common situation in cell physiology. By the sequential use of MuVal and CNA signaling, the models of the networks can be simulated in terms of multi-valued logic with graded-inhibitory (or activation) responses. MuVal provides an effective alternative to the currently applied assumptions of concerted or independent inhibitory mechanisms, which lead to false inferences in “classical” Boolean (or multi-valued) treatment if the reactions analyzed are being influenced by several regulators simultaneously.
• Odefy — Odefy is a MATLAB and Octave compatible toolbox which a modeling technique called HillCube, a canonical method to convert boolean models into continuous ordinary differential equation (ODE) systems. HillCubes are based on multivariate polynomial interpolation and incorporate Hill kinetics which are known to provide a good approximation of the synergistic dynamics of gene regulation.
• PINT — New pathway databases generally display pathways by retrieving information from a database dynamically. Some of them even provide their pathways in SBML or other exchangeable formats. Integrating these models is a challenging work, because these models were not built in the same way. Pathways integration Tool (PINT) may integrate the standard SBML files. Since these files may be obtained from different sources, any inconsistency in component names can be revised by using an annotation editor upon uploading a pathway model. This integration function greatly simplifies the building of a complex model from small models. To get new users started, about 190 curated public models of human pathways were collected by PINT. Relevant models can be selected and sent to the workbench by using a user-friendly query interface, which also accepts a gene list derived from high-throughput experiments. The models on the workbench, from either a public or a private source, can be integrated and painted. The painting function is useful for highlighting important genes or even their expression level on a merged pathway diagram, so that the biological significance can be revealed. This tool is freely available.
• PK-Sim / MoBi — Systems biology software platform for multiscale physiological modeling and simulation with a focus on physiologically-based pharmokinetics and -dynamics (PBPK/PD) including interfaces to MATLAB and R. Available to academic researchers via a free non-commercial license.
• SBFC — The System Biology Format Converter (SBFC) aims is to provide a generic framework that potentially allows any conversion between two formats. Interoperability between formats is a recurring issue in Systems Biology. Although there are various tools available to convert models from one format to another, most of them have been independently developed and cannot easily be combined, specially to provide support for more formats. The framework is written in Java and can be used as a standalone executable. This is a collaborative project and we hope that developers will provide support for more formats by creating new modules.SBFC allows anyone to easily add new converters and to integrate existing converters with a minimum of changes.
• SBML Harvester — The SBML Harvester creates a complex ontology-based representation of SBML models, utilizing both the structure of the SBML model and the models' MIRIAM annotations. This representation can then be used for the consistency verification of SBML models as well as complex queries across both models and biomedical ontologies.
• SBML Reaction Finder — The SBML Reaction Finder retrieves and extracts individual chemical reactions from curated SBML models.
• SBML Translators — translators from SBML to a wide variety of other formats such as: •C / C++ / C# •Jarnac •Java •Matlab / Mathematica •XPP To name but a few. All translators are available from one UI.
• SBML2Antimony — Antimony2sbml and sbml2antimony convert models between the SBML and Antimony formats. See separate listing above for Antimony.
• SBML2APM — A large collection of SBML models is found in the Biomodels Database. To use these models in APM, they must first be converted with the following utility. Once converted, the model can be simulated through APM MATLAB, APM Python, or through a Web Interface.
• SBML2BioPax — SBML2BioPax is a tool to convert any SBML files into BioPax. It can create BioPax level 2 or BioPax level 3. It uses the MIRIAM annotations as well as the SBO terms present in the SBML model to improve the BioPAX file generated. The tool is developed inside the SBFC (http://sbfc.sourceforge.net/) framework.
• SBML2LaTeX — SBML2LATEX is a tool to convert files in the System Biology Markup Language SBML) format into LATEX files. A convenient online version is available, which allows the user to directly generate various file types from SBML including PDF, TeX, DVI, PS, EPS, GIF, JPG or PNG. SBML2LATEX can also be downloaded and used locally in batch mode or interactively with its Graphical User Interface or several command line options. The purpose of SBML2LATEX is to provide a way to read the contents of XML-based SBML files. This is helpful and important for, e.g., error detection, proofreading and model communication.
• SBML2NEURON — SBML2NEURON is a provisional implementation of an SBML to NEURON converter. This uses the Python bindings of libSBML to generate an NMODL file containing the model represented in a basic SBML file, which can then be inserted onto a section in NEURON for simulation. Note that only a restricted set of SBML elements are supported (see the notes), but it can be used to simulate some of the models in BioModels Database. This is a work in progress and will be developed further to allow closer integration between NeuroML and SBML in realistic neuronal models.
• SBML2Octave — SBML2Octave is a tool to convert any SBML files into Octave. It will create a .m file that should be usable inside MATLAB as well. It support all the SBML elements until SBML level 3 core 1 apart for delay. The tool is developed inside the SBFC (http://sbfc.sourceforge.net/) framework.
• SBML2SMW — CellDesigner plugin for extracting Celldesigner model information, storing this information to a Semantic Mediawiki server and context-sensitive restoring and integration of this information in a Celldesigner model.
• SBML2XPP — Converter between SBML and XPPAut or Oscill8.
• 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-shorthand — Specification and conversion tools for a simple human-readable shorthand notation for a subset of SBML. Used for rapid building of SBML models without using a sophisticated GUI tool.
• SBMLsqueezer — SBMLsqueezer generates kinetic equations for biochemical networks according to context of each reaction. When used as a plug-in for CellDesigner it uses the information from the SBGN representation of all network components. In the stand-alone mode, SBMLsqueezer evaluates the Systems Biology Ontology (SBO) annotations to extract this information. An online version of SBMLsqueezer is available that runs without instally any software on the local machine. The rate laws that can be produced by SBMLsqueezer include several types of generalized mass action; detailed and generalized enzyme kinetics, various types of Hill equations, S- and H-systems, and additive models for gene regulation. User defined settings specify which equation to apply for any type of reaction and how to ensure unit consistency of the model. Equations can be created using contextual menus. All newly created parameters are equipped with the derived unit and annotated with SBO terms if available and meaningful textual names. MathML is inserted directly into the SBML file. LaTeX or text export of ordinary differential equations is provided.
• sbmltidy — A wrapper around the tidy command-line utility that will reformat ("pretty-print") an SBML file.
• 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)
• semanticSBML — Create, check, visualize, retrieve, cluster, annotate, merge SBML models. The program includes a web based graphical user interface. For tool developers a programming interface (Python) and RESTful web-services are provided. It features advanced functions to edit MIRIAM and SBO terms. The latest version of semanticSBML is fully web based and can be accessed under http://semanticsbml.org/semanticSBML/simple/index
• SyBiL — SyBiL is short for Systems Biology Linker. Biological pathways, reaction and signaling networks are made publicly availabel in formats standardized to the Biological Pathway eXchange format (BioPAX). Simulation tools for biological pathways are standardized to other Markup languages such as Systems Biology Markup Language (SBML) and Virtual Cell Markup Language (VCML). To take full advantage of scientific advances requires the mapping and integration of simulation markup languages with BioPAX. Sybil is developed to convert models between BioPAX and SBML/VCML.
• UTKornTools — UTK/ORNL Bio-SPICE tool set (inactive)

• Arcadia — Arcadia is an open-source, light-weight, cross-platform, C++ desktop application designed for visualizing biological networks such as metabolic pathways. It automatically translates SBML files into SBGN maps (using additional semantic information such as SBO terms when available). The default layout can be improved semi-automatically, e.g. by "cloning" (duplicating) highly connected species, or focusing on the neighborhood around a given species or reaction. The resulting map can be saved in the SBML file itself (using the layout extension) or exported as a vector image (PDF or SVG)
• AVIS — AVIS is a Google gadget compatible web-based viewer of interactive cell signaling networks. AVIS is an implementation of AJAX (Asynchronous JavaScript with XML) with the usage of the libraries GraphViz, ImageMagic (PerlMagic) and overLib. AVIS provides web-based visualization of text-based signaling networks with dynamical zooming, panning and linking capabilities. AVIS is a cross-platform web-based tool that can be used to visualize network maps as embedded objects in any web page. AVIS was implemented for visualization of PathwayGenerator, a tool that displays over 4000 automatically generated mammalian cell signaling maps; NodeNeighborhood a tool to visualize first and second interacting neighbors of yeast and mammalian proteins; and for Genes2Networks, a tool to connect lists of genes and protein using background protein interaction networks.
• BiNoM Cytoscape Plugin — BiNoM is a Cytoscape plugin, developed to facilitate the manipulation of biological networks represented in standard systems biology formats (SBML, SBGN, BioPAX) and to carry out studies on the network structure. BiNoM provides the user with a complete interface for the analysis of biological networks in Cytoscape environment.
• CADLIVE — CADLIVE (Computer-Aided Design of LIVing systEms) is a comprehensive computational tool for constructing large-scale biological network maps, analyzing the topological features of them, and simulating their dynamics. Using CADLIVE, we rationally design a biological system at the molecular interaction level for an engineering purpose.
• CellDesigner — CellDesigner is a structured diagram editor for drawing gene-regulatory and biochemical networks. Networks are drawn based on the process diagram, with graphical notation system. CellDesigner supports simulation and parameter scan by an integration with SBML ODE Solver and Copasi. By using CellDesigner, users can browse and modify existing SBML models with references to existing databases (MIRIAM supported), simulate and view the dynamics through an intuitive graphical interface.
• CellNetAnalyzer — CellNetAnalyzer (CNA) is a package for MATLAB and provides a comprehensive and user-friendly environment for structural and functional analysis of biochemical networks. CNA facilitates the analysis of metabolic (stoichiometric) as well as signaling and regulatory networks solely on their network topology, i.e. independent of kinetic mechanisms and parameters. CNA provides a powerful collection of tools and algorithms for structural network analysis which can be started in a menu-controlled manner within interactive network maps. Recently, API functionalities have been added to enable interested users to call algorithms of CNA from external programs. Applications of CNA can be found in systems biology, biotechnology, metabolic engineering, pharmacology, microbiology, chemical engineering.
• COPASI — COPASI is a software application for simulation and analysis of biochemical networks and their dynamics. COPASI is a stand-alone program that supports models in the SBML standard and can simulate their behavior using ODEs or Gillespie's stochastic simulation algorithm; arbitrary discrete events can be included in such simulations. COPASI provides an C++ API with language bindings for Perl, python, R, Java, and Octave and is able to communicate with the Systems Biology Workbench COPASI carries out several analyses of the network and its dynamics and has extensive support for parameter estimation and optimization. COPASI provides means to visualize data in customizable plots, histograms and animations of network diagrams. Please see the COPASI detailed description for a complete list of features. (You can view the test results for this system in the SBML Test Suite Database.)
• CySBML — Summary: CySBML is a plugin for the work with SBML in Cytoscape having the following features: SBML import, support of the SBML Layout and Qualitative Model packages, navigation in network layouts based on SBML structure, access to MIRIAM and SBO-based annotations, and SBML validation. CySBML includes an importer for BioModels to load SBML from standard repositories. Availability and implementation: Freely available for non-commercial purposes via the Cytoscape plugin manager or for download at http://sourceforge.net/projects/cysbml/. Main purpose is an import of SBML with the semantic annotations available within the Cytoscape network visualization.
• Cytoscape — open source software platform for visualizing complex-networks and integrating these with any type of attribute data
• DBSolve — DBSolveOptimum is a free software for kinetic modeling of metabolic pathways, analysis, and fitting parameters to experimental data. The program has text-based user interface for model description and graphical interface for data analysis. In addition to standart algorithms of simulation (ODE solver, explicit solver, steady-state analysis) the software include also automated local sencetivity analysis, parameters optimization procedures and bifurcaion analysis. The last version of DBSolveOptimum includes advanced tool for data visualization.
• 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.
• FAME — The Flux Analysis and Modeling Environment (FAME) is the first web-based modeling tool that combines the tasks of creating, editing, running, and analyzing/visualizing stoichiometric models into a single program. Analysis results can be automatically superimposed on familiar KEGG-like maps. FAME is written in PHP and uses the Python-based PySCeS-CBM for its linear solving capabilities. It comes with a comprehensive manual and a quick-start tutorial, and can be accessed online at http://f-a-m-e.org/ .
• Genetic Network Analyzer — Genetic Network Analyzer (GNA) is a computer tool for the modeling, simulation, analysis and verification of genetic regulatory networks. The aim of GNA is to assist biologists and bioinformaticians in constructing a qualitative model of a genetic regulatory network from knowledge about regulatory interactions and gene expression data. GNA provides a variety of functions to analyze the steady-state and transient dynamics of the network, among other things by exploiting state-of-the-art model-checking tools.
• GNAT — GNAT is an open source MATLAB-based toolbox. It provides functions for reading, writing, manipulation, visualization and simulation of glycan structures and glycosylation reaction networks. It is written in MATLAB and Java. It is thus platform-independent. It has been tested in Windows (Windows 7), Linux (Ubuntu), and Mac OS (X Lion) platforms.
• iBioSim — The iBioSim tool supports the modeling, analysis, and design of genetic circuits with applications in both systems and synthetic biology. It includes editors to construct genetic circuit models (GCM), Systems Biology Markup Language (SBML) models (L2V4 and L3V1 supported), and labeled Petri net (LPN) models. Models can be constructed by hand, imported from model databases, or learned from experimental data. These models can be analyzed using a variety of ODE and stochastic simulators as well as Markov chain analysis. The efficiency of these analysis methods is enhanced using a variety of automatic reaction-based and logical abstractions. The analysis results can be plotted as graphs or visualized upon the genetic circuit schematic. (You can view the test results for this system in the SBML Test Suite Database.)
• iPathways — Explore biological pathways on your palm!! In comprehending the biological complexity of living systems in disease and healthy states, molecular pathway maps form an integral part of a researcher’s arsenal. iPathways, developed by The Systems Biology Institute, Tokyo, brings your pathways from the desktop to the device for the first time!! iPathways provides access to molecular maps constructed in CellDesigner™ , compatible with SBML (Systems Biology Markup Language) and SBGN( Systems Biology Graphical Notation) standards. Browse pathways from your account and explore publications and genes of interest. Features (1.1): - Register Free! or use a guest login - Navigate pathway information by tapping on a gene or protein molecule or a reaction box - View publications associated with a reaction by tapping the PUBMED id on a reaction - Explore genes of interest on IHOP or Entrez directly from your pathways
• JigCell — JigCell is a set of computational tools with user-friendly interfaces developed for studying complex biochemical regulatory systems in general and the cell cycle control system in particular. For example, The JigCell Model Builder (JCMB) aides the modeler in defining a system to be modeled using SBML with a novel spreadsheet interface, allowing a large amount of data to be displayed in an organized manner. The JigCell Run Manager (JCRM) allows a user to specify a set of specifications for simulation runs using a spreadsheet interface. JigCell Aggregation Connector has been designed to define models in terms of components, for the purpose of being combined in a larger model. JigCell also aims in parameter estimation. A parameter estimator (PET, Parameter Estimation Toolkit) takes a biological model, experimental data, and the relationship between the model and data. Using this information the parameter estimator uses numerical tools to vary the parameters to the model looking for the parameters that best fit the experimental data.
• 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 supports model archive formats SBML (import and export) and CellML (import only).
• KEGGtranslator — Nowadays, the KEGG PATHWAY database provides a widely used service for pathway-based information. It contains manually drawn pathway maps with information about the genes, reactions and relations contained therein. To store these pathways, KEGG uses an own XML-format (called “KGML”). Parsers and translators are needed to process the pathway maps for usage in other applications and algorithms. We have developed KEGGtranslator, which is an easy-to-use stand-alone application that can visualize and convert KGML formatted XML-files into multiple output formats. Unlike other translators, KEGGtranslator supports a plethora of output formats, is able to augment the information in translated documents (e.g., MIRIAM annotations) beyond the scope of the KGML document, and amends missing components to fragmentary reactions within the pathway to allow simulations on those. KEGGtranslator converts KEGG files (KGML formatted XML-files) to SBML, GML, GraphML, JPG, GIF, LaTeX, etc. KEGG pathways can be obtained from ftp://ftp.genome.jp/pub/kegg/xml/kgml
• MesoRD — MesoRD is a stochastic and deterministic simulator of coupled chemical reactions and diffusions in space.
• MetaFluxNet — MetaFluxNet is a program package for managing information on the metabolic reaction network and for quantitatively analyzing metabolic fluxes in an interactive and customized way, which allows users to interpret and examine metabolic behavior in response to genetic and/or environmental modifications. As a result, quantitative in silico simulations of metabolic pathways can be carried out to understand the metabolic status and to design the metabolic engineering strategies.
• MetExplore — A web server to link metabolic experiments and genome-scale metabolic networks. MetExplore contains original network filters, allows to export in SBML and visualise filtered metabolic networks, and map masses from metabolic experiments onto complete metabolic networks. It also contains some graph-based methods to enrich the analyses.
• MOOSE — MOOSE 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 NeuroML.
• NetBuilder' — NetBuilder' is a software tool that is intended to help experimentalists creating and manipulating the mathematical representations they need to predict the behaviour of their systems. NetBuilder' has a graphical user interface, which allows its users to create a picture of the (known) components and interactions in the system, and enter quantitative information, such as know or estimated quantities and rates. A (hidden) translator converts the picture and the other data into a mathematical description, whereupon NetBuilder's "simulation engine" may be used to find out how the modelled system responds to changing input.
• Omix — an editor for metabolic network diagrams and a customizable visualization framework. With Omix, high quality diagrams can be created, suitable for publication and presentation. For this, Omix is designed towards the standards in user-guidance as known from the most important graphics software tools. Thus, a fast access to the functionalities of the software is warranted even for newcomers. Omix allows the design of metabolic network diagrams according the established network layout standards. For this, semi-automatic network drawing techniques support and accelerate the manual drawing process. Furthermore, Omix comes up with extensive visualization features. Any kind of data coming from experiment and simulation can be visualized with Omix. The way, data is visualized in Omix can completely be defined by the user because Visualization takes place in a scripting language called OVL (Omix Visualization Language). OVL allows changing the visual properties of network components. In this way, multi-omics data can be visualized by being mapped on the appearance of network components and their connections. Furthermore, user-interaction can be defined in OVL. Another visualization technique realized in Omix is Visualization on Demand, allowing the network-integrated visualization of multiple, hierarchical organized information in an interactive manner. Omix is equipped with a plug-in interface. Thus, the functionality of the software is extensible. Many plug-ins have been developed in recent years allowing network import from KEGG, im- and export of GML and SBML files as well as Modelica and Matlab code, network analysis tools such as elementary flux modes, flux balances and free fluxes, export of flash animations, data import from excel spreadsheets and much more.
• PaVESy — Pathway Visualization Editing System. Java based. (Linux/Mac/Win). Free download.
• PET — Parameter optimization and exploration is the primary feature of PET. Some of the other tasks PET can perform are simulations, setting up multiple experiments for a model, comparing parameter sets, and exporting plots for presentations.
• PK-Sim / MoBi — Systems biology software platform for multiscale physiological modeling and simulation with a focus on physiologically-based pharmokinetics and -dynamics (PBPK/PD) including interfaces to MATLAB and R. Available to academic researchers via a free non-commercial license.
• ProcessDB — ProcessDB helps molecular cell biologists manage and test their increasingly complex mechanistic hypotheses. ProcessDB does this with a bio-savvy graphical user interface that helps users formulate, visualize, compare, modify, manage and test their own mechanistic theories of cellular function. All models in ProcessDB can be automatically combined with user-specified experimental protocols and exported to the Berkeley Madonna solver for testing against experimental data. ProcessDB allows investigators to know with precision what their theories predict, and speeds discovery of mechanisms that account for all of the available data.
• ProMoT — The process modeling tool ProMoT is a software for the set-up and manipulation of models of complex technical or biological systems. Key features are the support of modular models, modeling libraries for different application areas, efficient and robust numerical algorithms, a own modeling language MDL 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.
• PySCeS — PySCeS: the Python Simulator for Cellular Systems is an extendable toolkit for the analysis and investigation of cellular systems. PySCeS is developed in Python and has been designed to be used both interactively or as a library. It utilises a human readable, model description language for describing models as well as being SBML compatible. PySCeS includes stoichiometric, simulation, steady state and Eigen analysis using direct non-linear root finders. It also includes full support for Metabolic Control Analysis (MCA), the characterisation of static bifurcations, multidimensional parameter scanning and 2/3D graph capabilities. Currently an extension PySCeS-CBM is being developed that allows for the interactive manipulation, modelling and optimization of genome scale, constraint based models (e.g. flux balance analysis)
• SBML Layout — SBML Layout encompasses: 1. a online application for layouting / rendering an SBML file , 2. a library for reading / writing SBML Layout and Rendering information as well as SBGN-ML and 3. a standalone application for displaying files with the SBML Layout or Rendering information. It is written in .net and available under the BSD for all platforms.
• SBML2TikZ — SBML2TikZ provides automatic generation of TeX Macros to illustrate Systems Biology Markup Language (SBML) graphs. The rendering is dependent on the SBML Render Extension proposed by Gauges et al. and the rendering library is built on the existing SBML Layout Library.
• 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)
• SBW: Auto Layout — The SBW AutoLayout module automatically creates lucid layouts of biochemical models. The SBW AutoLayout module has a graphical user interface (GUI) and an application programming interface (API). The GUI provides a typical window application for using AutoLayout's functionality, while the API allows programmers to incorporate AutoLayout's functionality into their own programs
• semanticSBML — Create, check, visualize, retrieve, cluster, annotate, merge SBML models. The program includes a web based graphical user interface. For tool developers a programming interface (Python) and RESTful web-services are provided. It features advanced functions to edit MIRIAM and SBO terms. The latest version of semanticSBML is fully web based and can be accessed under http://semanticsbml.org/semanticSBML/simple/index
• SimBiology — SimBiology ® is a MATLAB ® product from MathWorks that provides graphical and programmatic tools for computational systems biology and pharmacokinetics. It contains functionality for creating, simulating, and analyzing biological models. The SimBiology desktop lets you build a model using a block diagram editor, a model wizard, or a tabular interface. You can also create a model at the command line or directly from SBML files. SimBiology lets you simulate a model using stochastic or deterministic solvers. The product supports parameter estimation, sensitivity analysis, parameter scans, and other model analysis methods. All SimBiology features can be used together with the MATLAB programming language, letting you customize models, create or modify analysis tasks, and automate your workflow.
• Simulate3D — Traditionally simulation results are available as either data tables or X-Y plots. Data tables are helpful for further processing by other computational tools. X-Y plots, on the other hand, tend to get complex even for a limited number of species. In creating a new visualization tool, we had two goals in mind. A first goal was to tie simulation results strongly to the model. A next goal was to be able to view the simulation in real time to refine or broaden it where necessary. These goals have been realized in form of a 3D Time-course Visualization module.
• SimWiz — Visualizes simulation outputs from tools such as Copasi and STODE. (Linux/Win) (European Media License)
• Snoopy — a software tool to design and animate hierarchical graphs, among others Petri nets. To investigate biomolecular networks, Snoopy provides a unifying Petri net framework comprising a family of related Petri net classes. Models can be hierarchically structured, allowing for the mastering of larger networks. To move easily between the qualitative, stochastic and continuous modelling paradigms, models can be converted into each other. We get models sharing structure, but being specialized by their kinetic information. The analysis and iterative reverse engineering of biomolecular networks is supported by the simultaneous use of several Petri net classes, while the GUI adapts dynamically to the active one. Built-in animation and simulation are complemented by exports to various analysis tools.
• SurreyFBA — SurreyFBA provides constraint-based simulations of genome scale metabolic networks in a free, stand-alone software. In addition to basic simulation protocols the tool also implements the analysis of minimal substrate and product sets, which is useful for metabolic engineering and prediction of nutritional requirements in complex in vivo environments. The SurreyFBA is based on a command line interface to the GLPK solver distributed as binary and source code for the three major operating systems. The sfba command line tool, implemented in C++, is easily executed within scripting languages used in the bioinformatics community and provides efficient implementation of tasks requiring iterative calls to the linear programming solver. SurreyFBA includes JyMet, a graphics user interface allowing spreadsheet based model presentation, visualization of numerical results on metabolic networks represented in the Petri net convention, as well as in charts and plots.
• SYCAMORE — SYCAMORE is a system that provides you with a faciliated access to a number of tools and methods in order to build models of biochemical systems, view, analyse and refine them, as well as perform quick simulations.
• Systrip — Systrip is a visual environment for the analysis of time-series data in the context of biological networks. This software gathers bioinformatics and graph theoretical algorithms that can be assembled in different ways to help biologists in their visual mining process. Main features : 1. SBML file import and export. 2. Multiple kind of metabolic network representations (3D, force directed, biological convention preserving, hierachical ...). 3. Both graph theoritical measures and metabolic network analysis algorithms (choke points, scope, centrality...). 4. Time-series data import and visualization (table view, parallel coordinates, scatter plot). 5. Visualization of time-series in the context of the metabolic network. 6. 3D molecular visualization. 7. Database querry tools (Kegg, PublicHouse).
• The Cell Collective — The Cell Collective allows laboratory scientists working in different areas of the cell to collectively integrate their knowledge and create large-scale (rule-based) computational models of biological/biochemical networks in a non-technical fashion. Models created in the Cell Collective can be published and made available to the whole community, or shared with a selected group of collaborators, or completely kept private. The software provides an environment not only for the construction and sharing of computational (rule-based) models, but also for real-time, interactive simulations, as well as automated experiments consisting of hundreds of simulations.
• TinkerCell — TinkerCell is a drawing tool for synthetic biology that supports modular models and is highly extensible. One of the extensions is the COPASI C++ library, which adds most of the analysis capabilities from COPASI. Another extension support SBML import/export as well as the Antimony model definition language. TinkerCell supports over 200 Python and Octave functions, allowing users to add plug-ins written in Python or Octave. Users can also upload their plug-in to a central repository (hosted at Sourceforce); all other TinkerCell users will automatically get this plug-in in TinkerCell in the form of a new button. Hierarchical modeling is another key feature in TinkerCell, which is used in conjunction with a custom ontology for automatically generating one or more models from conceptual diagrams.
• VANTED — This system makes it possible to load and edit graphs, which may represent biological pathways or functional hierarchies. It is possible to map experimental datasets onto the graph elements and visualize time series data or data of different genotypes or environmental conditions in the context of a the underlying biological processes. Built-in statistic functions allow a fast evaluation of the data (e.g. t-Test or correlation analysis). Vanted can be extended for various functionalities, e.g. flux simulation, database access and 3D visualisation.
• Wolfram SystemModeler — Wolfram SystemModeler is a high-fidelity modeling software based on the Modelica language. It allows for hierarchical, multidomain, and hybrid systems modeling using a graphical drag and drop environment, and/or an equation based textual interface. And it integrates with the Wolfram technology platform to enable modeling, simulation, and analysis (of many types), all together achieving an agile design optimization loop. Provided with SystemModeler is a large set of built-in model libraries, including the BioChem library - an SBML compatible Modelica library designed for biochemical systems. By making use of the BioChem library, SystemModeler lets you build, simulate, and visualize PKPD and systems biology models. The software also provides SBML import and export functionality to allow Modelica-SBML model exchange.

Authors

Frank T. Bergmann, Bruce E. Shapiro and Mike Hucka.