Virtual Cell (VCell) is an

open-source Open source is source code that is made freely available for possible modification and redistribution. Products include permission to use the source code, design documents, or content of the product. The open-source model is a decentralized sof ...

software platform for modeling and simulation of living organisms, primarily

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

. It has been designed to be a tool for a wide range of scientists, from experimental cell biologists to theoretical biophysicists.

Concept

Virtual Cell is an advanced software platform for modeling and simulating reaction kinetics, membrane transport and diffusion in the complex geometries of cells and multicellular tissues. VCell models have a hierarchical tree structure. The trunk level is the "Physiology" consisting of compartments, species and chemical reactions, and reaction rates that are functions of concentrations. Given initial concentrations of species, VCell can calculate how these concentrations change over time. How these numerical simulations are performed, is determined through a number of "Applications", which specify whether simulations will be deterministic or stochastic, and spatial or compartmental; multiple "Applications" can also specify initial concentrations, diffusion coefficients, flow rates and a variety of modeling assumptions. Thus "Applications" can be viewed as computational experiments to test ideas about the physiological system. Each "Application" corresponds to a mathematical description, which is automatically translated into the VCell Math Description Language. Multiple "Simulations", including parameter scans and changes in solver specifications, can be run within each "Application". Models can range from the simple to the highly complex, and can represent a mixture of experimental data and purely theoretical assumptions. The Virtual Cell can be used as a distributed application over the Internet or as a standalone application. The graphical user interface allows construction of 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. Users may save their models in the VCell DataBase, which is maintained on servers at U. Connecticut. The VCell Database uses an access control system with permissions to allow users to maintain their models private, share them with select collaborators or make them public. The VCell website maintains
searchable list of models
that are public and associated with research publications. VCell Model Specification and Simulation Methods

VCell Model Specification and Simulation Methods

Features

VCell supports the following features: * Within the "Physiology", models can be specified as reaction networks or reaction rules. *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 In classical mathematics, analytic geometry, also known as coordinate geometry or Cartesian geometry, is the study of geometry using a coordinate system. This contrasts with synthetic geometry. Analytic geometry is used in physics and engineerin ...

equations, derived from combination of simple shapes or derived from imported images, such as 3D confocal microscope stacks. Utilities for 3D segmentation of image data into regions such as nucleus, mitochondria, 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 In mathematics, a partial differential equation (PDE) is an equation which imposes relations between the various partial derivatives of a Multivariable calculus, multivariable function. The function is often thought of as an "unknown" to be sol ...

(PDE) solvers, 4 non-spatial

stochastic Stochastic (, ) refers to the property of being well described by a random probability distribution. Although stochasticity and randomness are distinct in that the former refers to a modeling approach and the latter refers to phenomena themselv ...

solvers and Smoldyn for stochastic spatial simulations. VCell also offers a hybrid deterministic/stochastic spatial solver for situations where some species are present in low copy number and others are present in high copy number. Most recently, a network free solver
NFSim
was made available for stochastic simulation of large combinatorially complex rule-based models. Most solvers can be run locally, all solvers can be run remotely on VCell servers. * For compartmental deterministic models, the best parameter values to fit experimental data can be estimated using algorithms developed by the

COPASI COPASI (COmplex PAthway SImulator) is an open-source software application for creating and solving mathematical models of biological processes such as metabolic networks, cell-signaling pathways, regulatory networks, infectious diseases, and many ...

software system. These tools are available in VCell. * Models and simulation setups (so-called Applications) can be stored in local files as Virtual Cell Markup Language (VCML) or stored remotely in the VCell database. * Models can be imported and exported as Systems Biology Markup Language (SBML) *

Biological pathway A biological pathway is a series of interactions among molecules in a cell that leads to a certain product or a change in a cell. Such a pathway can trigger the assembly of new molecules, such as a fat or protein. Pathways can also turn genes on a ...

s can be imported as Biological Pathway Exchange (BioPAX) to build and annotate models.

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 BioModels is a free and open-source repository for storing, exchanging and retrieving quantitative models of biological interest created in 2006. All the models in the curated section of BioModels Database have been described in peer-reviewed scie ...

. *

s can be imported fro
Pathway Commons
* Model elements can be annotated with IDs from Pubmed UniProt ( proteins) KEGG (reactions and species) GeneOntology (reactions and species), Reactome (reactions and species) and ChEBI (mostly small molecules).

Development

The Virtual Cell is being developed at th
R. D Berlin Center for Cell Analysis and Modeling
at the University of Connecticut Health Center. The team is primarily funded through research grants through the National Institutes of Health.

References

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External links