Virtual Cell and CellML

1. Virtual Cell and CellML The Virtual Cell Group Center for Cell Analysis and Modeling University of Connecticut Health Center Farmington, CT – USA.

2. Outline • Virtual Cell – a brief introduction • Current CellML support in VCell • Issues • Possibility of using CellML API • Requirements for libCellML … • Acknowledgements 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! CellML Workshop 2007 - The Virtual Cell

4. External Resources • pathway databases • existing literature Physiological Model Extracellular Cytosol Nucleus A+B C ER Experiment D Fluxes Modeling & Analysis Species Reactions Structures Currents Model Application (maps to experimental context) Structures mapped to Subdomains Map reactions, fluxes, and currents Init Condn Boundary Condn Diffusion protocols Math Mapping • Sim Results • time response • sensitivities • steady state • Math • Description • Equations • Domains Subdomains (Image Regions) • Simulation (job) • Model Parameters • Mesh • Solver options Solver Services Geometry VCell Modeling Process CellML Workshop 2007 - The Virtual Cell

5. Applications Applications Applications Math Description Math Description Math Description Applications Physiology Topology Geometry, Initial Conditions, Boundary Conditions, Diffusion Coefficients, Pseudo-steady, Enable/Disable Reactions Topology Geometry, Initial Conditions, Boundary Conditions, Diffusion Coefficients, Pseudo-steady, Enable/Disable Reactions Topology Geometry, Initial Conditions, Boundary Conditions, Diffusion Coefficients, Pseudo-steady, Enable/Disable Reactions Topology Geometry, Initial Conditions, Boundary Conditions, Diffusion Coefficients, Pseudo-steady, Enable/Disable ReactionsElectrophysiology Protocols Molecular Species Compartment Topology VCMDL Simulations Simulations Simulations Images Images Images Timestep, Mesh Size, Parameter Searches, Sensitivity Timestep, Mesh Size, Parameter Searches, Sensitivity Timestep, Mesh Size, Parameter Searches, Sensitivity Images Results Results Results Reactions and Fluxes CellML Workshop 2007 - The Virtual Cell

6. What can we simulate? Math and Physics 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) 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 CellML Workshop 2007 - The Virtual Cell

9. New Physics Layer VCell Geometry VCell Application VCell Math Layer Solvers VCell Physiology 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) 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 !! 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??) !! 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 CellML Workshop 2007 - The Virtual Cell