Virtual Cell

Virtual Cell (VCell)^[1][2] is an open-source software platform for modeling and simulation of living organisms, primarily cells. It has been designed to be a tool for a wide range of scientists, from experimental cell biologists to theoretical biophysicists.^[3]

Concept

The primary mode of operation is the definition of a model consisting of compartments, species and chemical reactions, and reaction rates that are functions of concentrations. Given initial concentrations of species, the VCell can calculate how these concentrations change over time.

Models can range from the simple to the highly complex, and can represent a mixture of experimental data and purely theoretical assumptions.

Users access Virtual Cell as a distributed application over the Internet. The web-based Java interface allows users to build complex models in biologically relevant terms: compartment dimensions and shape, molecular characteristics, and interaction parameters. VCell converts the biological description into an equivalent mathematical system of differential equations. Users can switch back-and-forth between the schematic biological view and the mathematical view in the common graphical interface. Indeed, if users desire, they can manipulate the mathematical description directly, bypassing the schematic view. VCell allows users a choice of numerical solvers to translate the mathematical description into software code which is executed to perform the simulations. The results can be displayed on-line, or they can be downloaded to the user's computer in a wide variety of export formats. The Virtual Cell license allows free access to all members of the scientific community.^[4]

Features

VCell supports the following features:

• Simulations can be chosen to either resolve variations of concentrations over space (spatial simulations) or assume concentrations constant across compartments (compartmental simulations).
• For spatial simulations, geometries can be specified by analytic geometry equations, derived from combination of simple shapes or derived from imported images, such as 3D confocal microscope stacks. Utilities for segmenting image data into regions such as nucleus, cytosol and extracellular are provided.
• Simulations can be based on either integration of differential equations without use of random numbers (deterministic simulations) or be based on random events (stochastic simulations).
• Simulations can be run using a variety of solvers including: 6 ordinary differential equation (ODE) solvers, 2 partial differential equation (PDE) solvers, 4 non-spatial stochastic solvers and Smoldyn^[5] for stochastic spatial simulations. Choices between fixed and variable time steps exist. Some solvers can be run locally, all solvers can be run remotely on VCell servers.
• For compartmental determinsitc models, the best parameter values to fit experimental data can be estimated using algorithms developed by the COPASI software system. These tools are available witihin VCell.
• Models and simulation setups (so-called Applications) can be stored in local files as Virtual Cell Markup Language (VCML)^[6] or stored remotely in the VCell database.
• Models can be imported and exported as Systems Biology Markup Language (SBML)^[7]
• Biological pathways can be imported as Biological Pathway Exchange (BioPAX)^[8] to build and annotate models. A VCell prototype (to be released as Beta in April 2012) also can import quantitative data as Systems Biology Pathway Exchange (SBPAX).^[9]

Biological and related data sources

VCell allows users integrated access to a variety of sources to help build and annotate models:

• Models stored in the VCell database can be made accessible by their authors to some users (shared) or all users (public).
• VCell can import models from the BioModels Database.^[10]
• Biological pathways can be imported from Pathway Commons.^[11]
• Data on chemicals can be imported from UniProt (proteins)^[12] and ChEBI (mostly small molecules).^[13]
• A VCell prototype (to be released as Beta in April 2012) can import quantitative data from Signaling Gateway Molecule Pages^[14] and the SABIO-Reaction Kinetics Database.^[15]

Development

The Virtual Cell is being developed at the Center for Cell Analysis and Modeling at the University of Connecticut Health Center.^[16] The team is primarily funded through research grants through the National Institutes of Health.

References

External links

• VCell home page
• VCell user forum
• VCell Model Database
• Tutorial about using VCell to simulate Fluorescence recovery after photobleaching (FRAP), on YouTube.