Virtual Cell and Cell ML The Virtual Cell

Virtual Cell and Cell. ML The Virtual Cell Group Center for Cell Analysis and Modeling University of Connecticut Health Center Farmington, CT – USA. 04/04/2007 Cell. ML Workshop 2007 - The Virtual Cell

Outline Virtual Cell – a brief introduction n Current Cell. ML support in VCell n Issues n Possibility of using Cell. ML API n Requirements for lib. Cell. ML … n Acknowledgements n 04/04/2007 Cell. ML Workshop 2007 - The Virtual Cell 2

The Virtual Cell n What is it? q n What can it do? q q q n q 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? q q n At http: //www. vcell. org What do you need to run it? q n Modeling reactions, diffusion, membrane transport, flow, electrical potential and currents Compartmental or spatial simulations (1 D, 2 D, 3 D) on analytical or image-based geometries Collaborative work (shared database) and interoperability (SBML, Cell. ML, data formats) Where can you get it? q n It is a tool to build models and run simulations of cellular processes Email vcell_support@uchc. edu The website (user guide, tutorials, technical info, examples) What new features are expected in the near future? q q q 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 Cell. ML Workshop 2007 - The Virtual Cell 3

VCell Modeling Process External Resources • pathway databases Physiological Model Extracellular • existing literature Cytosol Nucleus ER A+B C Experiment D Fluxes Species Reactions Structures Currents Structures Map reactions, fluxes, and mapped to currents Subdomains Init Condn Boundary Condn Diffusion protocols Model Application (maps to experimental context) Subdomains (Image Regions) Geometry 04/04/2007 Modeling & Analysis Math Mapping Math Description • Equations • Domains Simulation (job) • Model Parameters • Mesh • Solver options Cell. ML Workshop 2007 - The Virtual Cell Sim Results • time response • sensitivities • steady state Solver Services 4

Physiology Molecular Species Compartment Topology Reactions and Fluxes 04/04/2007 Applications Topology Geometry, Initial Conditions, Boundary Geometry, Conditions, Diffusion Initial Conditions, Coefficients, Pseudo-steady, Initial Conditions, Boundary Conditions, Enable/Disable Reactions Boundary Conditions, Diffusion Coefficients, Electrophysiology Protocols Diffusion Coefficients, Pseudo-steady, Enable/Disable Reactions Images Cell. ML Workshop 2007 - The Virtual Cell Math Description VCMDL Simulations Timestep, Mesh Size, Paramete Size, r Paramete Searches, r Searches, Sensitivity Results 5

What can we simulate? Math and Physics 04/04/2007 Cell. ML Workshop 2007 - The Virtual Cell 6

Current Scope and Future Plans n Intended Users q q n Modeling domain q q n Biologists Biophysicists/Mathematicians Compartmental or 1 D, 2 D, 3 D Geometry Reaction/Diffusion/Membrane Transport Electric Potential (electrophysiology) Advection and Membrane Diffusion Future q q q q q 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 Open. Source) 04/04/2007 Cell. ML Workshop 2007 - The Virtual Cell 7

Current support for Cell. ML in Virtual Cell n Incomplete support for Cell. ML q q n Parsing of XML DOM object from Cell. ML and translating into appropriate VCell equivalent object q q n Export non-spatial biomodels and non-spatial math models to Cell. ML 1. 0 Hasn’t been actively maintained Cumbersome process Can be inconsistent Does not export electrophysiological models 04/04/2007 Cell. ML Workshop 2007 - The Virtual Cell 8

Issues to consider n New Physics-oriented layer in VCell q q n 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 Cell. ML after determining causality (identify solvable form of equations and all state variables) VCell Geometry VCell Physiology 04/04/2007 New Physics Layer VCell Application Cell. ML Workshop 2007 - The Virtual Cell VCell Math Layer Solvers 9

Using the Cell. ML API n n n Using the. idl files in the Cell. ML API package, generated the Java interface stubs Seems to provide the necessary functionality to create a Cell. ML document Problem : q q n Implementation of the Java interfaces and client necessary! Possible, but time-consuming Non-CORBA JNI (Java) Binding will be extremely helpful !! 04/04/2007 Cell. ML Workshop 2007 - The Virtual Cell 10

What do we need? …. n Simple library to read, write, manipulate Cell. ML models q q n similar to lib. SBML we will have our own internal Cell. ML compatible representation With Java bindings, supporting Windows, Linux, Mac platforms Simple methods to add/extract Cell. ML model constructs transparency from XML syntax Looking forward to the release of the non-CORBA JNI (Java) Binding for Cell. ML-API (soon? ? ) !! 04/04/2007 Cell. ML Workshop 2007 - The Virtual Cell 11

Acknowledgements We would like to thank Cell. ML consortium for providing this opportunity to present our computational cell biology tool to the Cell. ML community n Our sincere thanks to David Nickerson for making the presentation on our behalf n 04/04/2007 Cell. ML Workshop 2007 - The Virtual Cell 12