ST NetWatch: Modeling Tools

AgentCell (Digital E. Coli)
This site provides access to a simulation tool for studying bacterial chemotaxis in the absence and presence of a gradient to understand how intracellular signaling events control cellular behavior. The software is freely available and the site includes several animations showing digital chemotaxis using AgentCell.
Arkin Lab
The Arkin lab is developing modeling and simulation tools for the analysis of biological signaling networks. The "Research" and "Tools" sections of the site provide particularly useful information from tutorials and excerpts from presentations on applying mathematical analysis to biological questions to actual software available to download to perform analysis. Arkin's group provides information for both novices and experienced biological computational scientists.
AVIS is an AJAX (Asynchronous JavaScript and XML) viewer for cell signaling networks, gene regulatory networks, or protein interaction networks, which provides web-based visualization of cellular networks with dynamic zooming, panning, and linking capabilities. AVIS will render data describing interaction networks in various text file formats. There are samples on the site or you can read the manual to find out how to format your own network into a compatible file. A detailed user manual explains the acceptable file formats (SIG, Pajek NET, AVIS, or SBML), how to run AVIS on a server, how to add the AVIS Gadget to web pages, and how to configure AVIS for customized web display of networks. The tool can also be used directly on the Iyengar lab's web site to visualize networks, by uploading a file in an acceptable format (choose the link "Upload and visualize network text files from your client machine"). AVIS uses the GraphViz, ImageMagic (PerlMagic), and overLib libraries.
Bacterial Chemotaxis in Silico
The Physiology, Development, and Neuroscience (PDN) group at the University of Cambridge has developed several tools for studying chemotaxis in E. coli. The three different computational biology tools are BCT, StochSim, and Smoldyn. BCT is a text-based, deterministic simulator of the chemotaxis signal transduction pathway in E. coli. StochSim was originally designed as a stochastic simulator to study bacterial chemotaxis and can now be used for simulation of biochemical processes. Smoldyn stands for Smoluchowski dynamics and is a biochemical simulator in which the diffusion of molecules in 1-, 2-, or 3-dimensions can be computed and displayed graphically. Each of the programs is available for downloading and the algorithms are described in detail. The site also provide data related to the biochemical events associated with E. coli chemotaxis and pages discussion various aspect of bacterial chemotaxis.
BioModels Database
The BioModels Database, part of the EMBL-EBI collection of databases, is a repository for published mathematical models of biological pathways. Biochemical and signaling pathways are both included, but biochemical pathways are more highly represented. Some models (curated models) have been checked for accuracy by database curators, and others (non-curated models) have had only their mathematical elements verified. Users can search models in the database by author or contributor names, by InterPro or KEGG pathway ID, or by gene ontology terms. The models are annotated with links to publications, protein sequences from UniProt, and other information relevant to the pathway components. Models may be downloaded individually as needed, or the entire database of hundreds of models may be downloaded at once. The models are in Systems Biology Markup Language (SBML) format and ready for use in SBML-compatible simulators.
BioNetGen is a programming language for writing rule-based models of biological systems, such as metabolic and signaling networks, and associated software for running the models and analyzing the results of simulations. The BNGEditor software can be downloaded and used to develop, visualize, simulate, and analyze models using the BioNetGen language. RuleBender is another self-contained interface for developing models and running and analyzing simulations using the BioNetGen language, and the NFSim software is optimized for supporting agent-based simulations (models that describe the activities of networks with many autonomous agents). There are also Web-based and command-line interfaces for using BioNetGen. BioNetGen models may be exported to the Virtual Cell (VCell). An online tutorial and published models are available on the site, as is a detailed primer on rule-based modeling of signal transduction pathways. All BioNetGen software is open-source and freely available for users who have a username and password, and instructions for obtaining access are provided on the main page.
CellDesigner allows users to create and annotate graphical models of gene regulatory and biochemical networks from experimental interaction and kinetics data. You can build models from scratch or start from existing models that are available from the BioModels Database. CellDesigner can connect to databases such as PubMed, Entrez Gene, and the Saccharomyces Genome Database to retrieve information about pathway components. The CellDesigner software is available free of charge from its developer, the Systems Biology Institute, and is compatible with Systems Biology Markup Language (SBML) and the Systems Biology Workbench, a software platform that integrates diverse modeling tools so that they can be used together.
Cellerator is a tool that allows users to model interactions between components of a signal transduction network or between multiple networks. It is a plugin for Mathematica, a commercially available mathematical computation and visualization software package. Cellerator translates reaction data into differential equations that Mathematica can use for simulations and analysis. The Cellerator site has a list of suggested reading materials pertaining to systems biology and mathematical modeling and includes a gallery of images and movies generated by Cellerator. xCellerator is the second-generation version of the software that uses a different algorithm for translating data, which makes it faster than Cellerator, and is compatible with systems biology markup language (SBML). The xCellerator site includes sample models for NF-κB signaling, MAPK cascades, G protein activation, and circadian rhythms. Both Cellerator and xCellerator are open-source and freely available for academic use, although they will only function if users already have the Mathematica software.
CompuCell3D is an open-source tool for modeling both biological and physical processes. CompuCell3D does not analyze molecular dynamics; instead, it is used to run simulations and visualize biological processes at the level of individual cells or tissues. To create a CompuCell3D simulation, the user first specifies the cells involved in the process and assigns properties to the cells, such as size, response to an effector molecule, behavior in a chemical gradient, or secretion of a molecule. The user also specifies the interactions between cells and defines the initial starting conditions. Creating complex, biologically relevant models requires users to write their own Python scripts. The data generated by CompuCell3D simulations can be analyzed with programs like MatLab and Mathematica. A model of vertebrate somitogenesis constructed with CompuCell is available on the site, showing the distribution of a growth factor, cell adhesion molecules, and protein expression during vertebrate somitogenesis.
Cytoscape is an open source software platform for visualizing and annotating complex molecular interaction networks. The software supports the import of data in multiple file formats, and various options allow the user to customize the output graphs. Because Cytoscape is open source, users are encouraged to develop and share their own plugins to expand the software’s capabilities, and the site includes a tutorial for writing plugins. Many user-developed plugins are freely available, although many require users to register for a free license before downloading. These plugins enhance the functionality of Cytoscape by enabling the user to analyze network properties, apply filters to complex networks, add gene expression data to a network, or identify new networks. A description of each plugin, information about any restrictions that may apply to its use, and links to the site where it may downloaded are provided. Users can also subscribe to an email service that will notify them when new plugins become available.
Hierarchical Network Organisation (HiNO)
Gene expression networks are directed and hierarchical, and changing how information flows through the network affects the physiological outcome. Understanding the hierarchical relationships and interdependencies between components of regulatory networks is an important goal of systems biology. Hierarchical Network Organisation (HiNO) is a tool developed by Mara Hartsperger, and users may upload regulatory interaction data to acquire a visual representation of the hierarchical structure of their regulatory network of interest. The HiNO method is a modification of the breadth-first-search (BFS) method for determining the hierarchical structure of regulatory networks that aims to address the problem of misassigning nodes to the incorrect level within the hierarchy. The Help section includes instructions for formatting input and interpreting output.
MCell is "A General Monte Carlo Simulator Of Cellular Microphysiology" and is simulation software designed to incorporate high resolution ultrastructure into models of ligand diffusion and signaling. The software was developed by Thomas M. Bartol Jr. at the Salk Institute and Joel R. Stiles at the Pittsburg Supercomputing Center.
ModelDB is part of SenseLab, which consists of several interconnected databases: the Cell Properties Database (CellPropDB), Neuron Database (NeuronDB), Model Database (ModelDB), Olfactory Receptor Database (ORDB), Odor Molecular Database (OdorDB), Olfactory Bulb Odor Map Database (OdorMapDB), Microcircuit Database (MicrocircuitDB), and BrainPharm. ModelDB is a collection of published computational neuroscience models that users can download and execute with the free, open source simulator Neuron.
Modeller is a tool for comparative modeling of three-dimensional protein structures. To generate a model, the user submits an alignment of the sequences to be modeled and a structure on which to model the sequences. Users at academic and nonprofit institutions may download the Modeller software at no charge after completing a license agreement. A list of frequently asked questions (FAQ), a user-editable wiki, tutorials, and a user manual are available in the Discussion Forum and Documentation sections of the site. Modeller was created and is maintained by Andrej Sali’s lab at the University of California, San Francisco. Other protein structure modeling tools from the Sali lab include ModBase, a database of theoretically calculated comparative protein structure models; ModWeb, a Web-based tool for protein structure modeling; ModLoop, a Web-based tool for modeling loops in protein structures; and ModEval, a Web-based tool for evaluating protein structure models generated with the Modeller software.
The dynamics and topology of a network are influenced by the underlying structure of the network and its modules, which are groups of components that exert greater influence on one another than they do on other components of the network. Components may be members of multiple modules, and identifying overlapping modules within networks rapidly and accurately is a persistent problem in systems biology. Members of the LINK-Group, a consortium of researchers interested in network topology and dynamics, developed ModuLand, a set of algorithms for identifying overlapping modules within a network. The site includes detailed documentation describing how the algorithms were developed and how to use them. The algorithm package may be downloaded after completing a free online license, and running the programs requires a Linux-based operating system.
Nerve is a program that simulates action potential generation and propagation. The program allows users to alter various parameters to determine their effects on action potential propagation.
NEURON is a simulation environment for developing and exercising models of neurons and networks of neurons. Michael Hines and John W. Moore at the Department of Neurobiology, Duke University have collaborated in its creation. The software is freely available for downloading.
PyMOL is an open-source software package for rendering high-resolution 3D structures of biomolecules. Users can import data in various file types, including PDB and PubChem files and volumetric electron density maps. Structures can be rendered as line or ribbon diagrams or space-filling models. Structures can be animated or used to model ligand binding, and PyMOL data can be exported in Virtual Reality Markup Language (VRML) for creating movies or making physical models with a 3D printer. PyMOL images and animations can be embedded into Powerpoint presentations with the AxPyMOL plugin. The PyMOL Wiki is maintained by users and includes FAQs, tutorials, a library of user-generated scripts and plugins, a command glossary, and a gallery of images created with PyMOL. Free educational subscriptions for PyMOL are available for full-time students and educators. Academic professionals may purchase annual subscriptions for AxPyMOL only or for both PyMOL and AxPyMOL.
(Subscribed Site)
RVBI Cytoscape Plugins
The Resource for Biocomputing, Visualization, and Informatics (RVBI) at the University of California, San Francisco (UCSF), has developed various plugins for the open-source Cytoscape network analysis and visualization platform. The site includes many different types of plugins that expand and augment the basic functionality of Cytoscape. For example, the clusterMaker and clusterExplorer plugins allow users to create and use clustering algorithms to sort network data in Cytoscape. The structureViz plugin enables users to link Cytoscape networks with molecular structures generated with the UCSF Chimera software. Instructions for installing and using the many available plugins are provided on the site.
Simmune Project
The Simmune Project from the National Institute of Allergy and Infectious Disease (NIAID) aims to develop systems biology tools that bridge the gap between the different modeling approaches taken by experimental and theoretical biologists. The Simmune software was originally developed at the University of Hamburg for simulating immunological events, but can be used for modeling events in other biological contexts. Users may incorporate data describing biological phenomena at different scales -- the molecular, cellular, and tissue levels. The Simmune software package consists of three components: the modeler (Simmod), the simulator (Simmune), and the Network Browser. Users define the components of the model with Simmod, including such information as the properties of individual molecules, how individual molecules interact, their rates of association and dissociation, properties of the cells and their environment, and other parameters for the in silico experiments. After the parameters of the model have been defined, the Simmune simulator runs simulations during which users can collect data from individual cells at specific time points. Users can explore the data captured during the simulation with the Network Browser. The software package is free for noncommercial use, and licenses are available for commercial users.
Systems Biology Markup Language (SBML)
SBML is an XML-based language for representing models of biochemical reaction networks, including signaling pathways, in computer-readable format. STKE has chosen an SBML-compatible file format for machine-readable versions of the Connections Maps database. The website provides assistive documents, schemas, and presentations, as well as a comprehensive FAQ list and two SBML discussion forums. Other highlights are an extensive model repository and a community-editable SBML Wiki area, where users can describe their own experiences with the software and make suggestions for future development. SBML tools include those for validation, visualization, and conversion of SBML files.
Systems Biology Workbench
One difficulty in mathematical modeling of pathways is integrating information from multiple sources, which are often in incompatible formats. The Systems Biology Workbench (SBW) is a software platform that allows users to integrate data from different types of programs and modeling tools. SBW provides a framework that enables applications that are normally incompatible to share information. SBW was designed to speed the time it takes to build new models from aggregated information or add to existing models without starting from scratch. SBW is especially useful because it allows users to take data from models in one format and put them into a model in a different format. SBW uses Systems Biology Markup Language (SBML), the format that is becoming the standard for modeling tools.
The Cell Collective
Building accurate models of the interconnected pathways that function within a cell is necessarily complicated and generally requires expertise in computational biology. The Cell Collective is a Web-based community platform for modeling cellular processes that was designed to be useful to biologists regardless of mathematical expertise or coding experience. Users may sign up for a free account to access existing models or create and edit their own models. Models that are under construction may be accessed only by the users who created them, but all Cell Collective users may access completed models. Real-time simulations on completed models allow users to visualize the dynamics of pathway components as the system runs under user-defined starting conditions and includes the ability to simulate gain and loss of functions within the pathway. There is also a tool for running in silico experiments (up to 100 simulations in parallel) with defined starting conditions. A video tutorial gives an overview of the site and how to use the tool to build, edit, and manipulate models.
The Virtual Cell
The Virtual Cell (VCell) is a Web-based computational tool for modeling and analyzing cell biology developed at the National Resource for Cell Analysis and Modeling (NRCAM) at the University of Connecticut Health Center. Models may be built from experimental data or based on theoretical assumptions. Users enter biological descriptions of the process they wish to model, and these parameters are converted into a mathematical model. These equations can then be used to run simulations, the results of which may be analyzed online or downloaded. A user guide and various tutorials provide instructions for interacting with and getting the most out of the application.
TinkerCell is a computer-aided design (CAD) tool that was designed to help synthetic biologists engineer biological systems by integrating pathway design with experimental results, information from databases, and mathematical modeling. TinkerCell is an open-source plug-in framework, so users can create new functions for the tool and share these with other users by uploading them into an online repository. Users construct pathway diagrams by first adding the components from a menu of component types (protein, RNA, small molecule, etc.) and assigning attributes to each component (functionality or subcellular localization, for example). The pathway construction software is modular, so components can be used to represent multistep processes or reactions. Users then define the relationships between the components--for example, whether one component transcriptionally represses another, biochemically activates another, or catalyzes a reaction involving another component. The plug-ins allow users to run simulations and map experimental data onto a model and enable users to refine their models through multiple rounds of simulation and editing. The TinkerCell repository includes preexisting modules that can be inserted into models as well as user-created plug-ins for analyzing models.
UCSF Chimera
UCSF Chimera was developed by the Resource for Biocomputing, Visualization, and Informatics (RBVI), which is funded by the National Institutes of Health (NIH) and National Institute of General Medical Sciences (NIGMS). The Chimera software enables users to render models of small molecules, nucleic acids, proteins, viruses, and multiprotein complexes. Many file types can be used as input and manipulated, including PDB and PubChem files, electrostatic potential data, and electron density maps. The software enables basic operations such as adding text labels to structures and changing how structures are represented—as line or ribbon diagrams, ball-and-stick or space-filling models, or other rendering styles. Chimera also enables more advanced operations such as predicting possible binding orientations given known ligand and receptor structures. An online user guide, an index of commands, and two types of tutorials give detailed instructions on using the software. Tutorials provide text and images illustrating common and advanced operations, and video tutorials show an expert user performing a manipulation while describing the process. Image and animation galleries showcase models rendered with Chimera. Chimera is free for noncommercial use.