Virtual Cell and CellML

The Virtual Cell GroupCenter for Cell Analysis and ModelingUniversity of Connecticut Health Center Farmington, CT – USA.

04/04/2007 CellML Workshop 2007 - The Virtual Cell

2

Outline

Virtual Cell – a brief introduction Current CellML support in VCell Issues Possibility of using CellML API Requirements for libCellML … Acknowledgements

04/04/2007 CellML Workshop 2007 - The Virtual Cell

3

The Virtual Cell What is it?

It is a tool to build models and run simulations of cellular processes What can it do?

Modeling reactions, diffusion, membrane transport, flow, electrical potential and currents

Compartmental or spatial simulations (1D, 2D, 3D) on analytical or image-based geometries

Collaborative work (shared database) and interoperability (SBML, CellML, data formats)

Where can you get it? At http://www.vcell.org

What do you need to run it? Java and an Internet connection (it runs over the web) It is free but you must register

Where can you find more info or get help? Email vcell_support@uchc.edu The website (user guide, tutorials, technical info, examples)

What new features are expected in the near future? Standalone, grid-based, resource-sharing versions Stochastics and brownian motion Filaments and structures Open source and plug-in architecture Components as web services Modeling the experiment… and much, much more!

04/04/2007 CellML Workshop 2007 - The Virtual Cell

4

VCell Modeling Process

Model Application(maps to experimental context)

Init CondnBoundary Condn

Diffusionprotocols

MathDescription•Equations•Domains

Sim Results•time response•sensitivities•steady state

Modeling &Analysis

Structures mapped to Subdomains

Subdomains (Image Regions)

Structures

Map reactions,fluxes, and

currents

SpeciesReactions

MathMapping

Experiment

External Resources • pathway databases• existing literature

Physiological ModelCytosol

ER

Nucleus

Extracellular

A+B C

D

GeometrySimulation (job)•Model Parameters•Mesh•Solver options

Solver Services

Fluxes

Currents

04/04/2007 CellML Workshop 2007 - The Virtual Cell

5

Applications

Topology Geometry,

Initial Conditions, Boundary Conditions, Diffusion Coefficients,

Pseudo-steady, Enable/Disable

Reactions

Images

Applications

Topology Geometry,

Initial Conditions, Boundary Conditions, Diffusion Coefficients,

Pseudo-steady, Enable/Disable

Reactions

Images

Applications

Topology Geometry,

Initial Conditions, Boundary Conditions, Diffusion Coefficients,

Pseudo-steady, Enable/Disable

Reactions

Images

Applications

Topology Geometry,

Initial Conditions, Boundary Conditions, Diffusion Coefficients,

Pseudo-steady, Enable/Disable

ReactionsElectrophysiology

ProtocolsImages

Math DescriptionMath DescriptionMath Description

VCMDL

Physiology

Molecular SpeciesCompartment Topology

Reactions and Fluxes

Simulations

Timestep,Mesh Size,ParameterSearches,Sensitivity

Results

Simulations

Timestep,Mesh Size,ParameterSearches,Sensitivity

Results

Simulations

Timestep,Mesh Size,ParameterSearches,Sensitivity

Results

04/04/2007 CellML Workshop 2007 - The Virtual Cell

6

What can we simulate?

iii Rt

C Fdiv

RT

FD=CzCCD iiiiiiiiii VF ,

CkBAkiR 11

k1 A + B C , k1

Math and Physics

04/04/2007 CellML Workshop 2007 - The Virtual Cell

7

Current Scope and Future Plans Intended Users

Biologists Biophysicists/Mathematicians

Modeling domain Compartmental or 1D, 2D, 3D Geometry Reaction/Diffusion/Membrane Transport Electric Potential (electrophysiology) Advection and Membrane Diffusion

Future Optimization & parameter scans Protocols Advection & Directed Transport Stochastic Processes Complexes Constraints & Virtual Experiments Stand-alone & grid-based versions Cell motility New architecture – plug-ins, modules, etc. (VCell OpenSource)

04/04/2007 CellML Workshop 2007 - The Virtual Cell

8

Current support for CellML in Virtual Cell Incomplete support for CellML

Export non-spatial biomodels and non-spatial math models to CellML1.0

Hasn’t been actively maintained

Parsing of XML DOM object from CellML and translating into appropriate VCell equivalent object Cumbersome process Can be inconsistent

Does not export electrophysiological models

04/04/2007 CellML Workshop 2007 - The Virtual Cell

9

Issues to consider New Physics-oriented layer in VCell

All modeling assumptions made explicit and mathematically complete (e.g. lumped vs distributed parameter model for the same mechanism)

Components described by equations, connected to form a system (causality may be left unspecified)

Compatible with CellML after determining causality (identify solvable form of equations and all state variables)

VCell PhysiologyVCell

Application

New Physics Layer

VCell Math Layer Solvers

VCell Geometry

04/04/2007 CellML Workshop 2007 - The Virtual Cell

10

Using the CellML API

Using the .idl files in the CellML API package, generated the Java interface stubs

Seems to provide the necessary functionality to create a CellML document

Problem : Implementation of the Java interfaces and

client necessary! Possible, but time-consuming

Non-CORBA JNI (Java) Binding will be extremely helpful !!

04/04/2007 CellML Workshop 2007 - The Virtual Cell

11

What do we need? ….

Simple library to read, write, manipulate CellML models similar to libSBML we will have our own internal CellML compatible

representation With Java bindings, supporting Windows, Linux, Mac

platforms Simple methods to add/extract CellML model

constructs - transparency from XML syntax Looking forward to the release of the non-CORBA

JNI (Java) Binding for CellML-API (soon??) !!

04/04/2007 CellML Workshop 2007 - The Virtual Cell

12

Acknowledgements

We would like to thank CellML consortium for providing this opportunity to present our computational cell biology tool to the CellML community

Our sincere thanks to David Nickerson for making the presentation on our behalf