1. The ERATO Systems Biology Workbench Hamid Bolouri ERATO Kitano Systems Biology Project California Institute of Technology & University of Hertfordshire, UK Project PIs: Hiroaki Kitano and John Doyle Software development team: Andrew Finney, Michael Hucka, Herbert Sauro Collaborators: Adam Arkin (BioSpice), Dennis Bray (StochSim), Igor Goryanin (DBsolve), Les Loew (VirtualCell), Pedro Mendes (Gepasi), Masaru Tomita (Ecell) Acknowledgements: Mark Borisuk, Eric Mjolsness, Tau-Mu Yi

3. Resource Sharing, Motivation Tool 7 Tool 3 Tool 4 Tool 2 Tool 6 Tool 5 Tool 1 Multistate reactions/stochastic Reaction/Diffusion Visualization of networks Optimization Bifurcation analysis Handle large systems Our goal: provide software infrastructure to enable sharing of simulation software (current and future) and collaboration between developers (and modelers!)

4. Signal transduction Motion Ligand binding Motor Example Workbench application: bacterial chemotaxis

19. ERATO Systems Biology Workbench: driving principles Integrate, don’t reinvent! –integrate existing simulators –use standard application integration methods object oriented, XML, Java and related technologies Accommodate future tools –minimize need for ad hoc solutions object oriented, XML, Java and related technologies –XML & API standards for future contributors Make sure contributors benefit –symmetric plug-in infrastructure –open source code infrastructure software –widen user-base, but protect IPR of contributors

23. Systems Biology Markup Language [SBML] A common XML format for biochemical networks Enables exchange of models between simulators Developed in collaboration with BioSpice, DBsolve, Gepasi, Jarnac, Ecell, StochSim, VirtualCell Available for public review since Sept 2000 at ftp://ftp.cds.caltech.edu/pub/caltech-erato/sbml/sbml.pdf Proposed extensions due 2 nd Quarter 2001

25. Example workbench plug-in modules Data filtering and preparation –e.g. image processing, regression, clustering Database support –e.g. web searching, storage management, translators, conflict resolution Model description tools –scripts, languages, schematic tools Model preprocessing –e.g. conserved quantities, redundancy removal Maths language / maths description support Equation solvers –e.g. ODE, DAE, PDE, stochastic Analysis tools –e.g. 2/3/4D graphing, bifurcation, MCA Optimization and parameter searching

26. Example potential plug-ins from DBsolve Data filtering and preparation –regression to implicit and explicit algebraic equations Database support –direct data import from WITT, MPW, KEGG Model description tools –stoichiometric matrix Model preprocessing –conserved quantities & redundancy removal Maths language / maths description support –maths editor Equation solvers –mixed ODE + NAE, LSODE Analysis tools –2D graphing, bifurcation, continuation, all steady states Optimization and parameter searching –Hooke & Jeeves, Levenburg-Marquardt

27. Systems Biology Workbench - APIs APIs provided by the Workbench for simulators –Will provide access to a spectrum of current tools –Integration into 3 rd party simulators will require: –SBML output –One menu item associated with one external library call –Available Q1 2001 –Lower level APIs for optimization, bifurcation, time-based simulation and data display will follow, Q2 2001 APIs provided by simulators to plug into Workbench –Existing collaborators no API conformance, we will interface to given APIs The minimum requirement: –Either parse SBML, parse equivalent documented format or provide a model construction API –Output some documented numeric format or structure –Future contributors to SBW Standard API for independent development available Q2 2001

29. Systems Biology Workbench - APIs APIs provided by the Workbench for simulators –Will provide access to a spectrum of current tools –Integration into 3 rd party simulators will require: –SBML output –One menu item associated with one external library call –Available Q1 2001 –Lower level APIs for optimization, bifurcation, time-based simulation and data display will follow, Q2 2001 APIs provided by simulators to plug into Workbench –Existing collaborators no API conformance, we will interface to given APIs The minimum requirement: –Either parse SBML, parse equivalent documented format or provide a model construction API –Output some documented numeric format or structure –Future contributors to SBW Standard API for independent development available Q2 2001

32. Workbench Development Plan TaskNovDecJanFebMarAprMay Design GUI and Simulation Engine (Sauro) Stochastic Simulation (Gibson) Bifurcation analysis (Goryanin) Param. optimization (Mendes) Multi-representation simulation Linux Port QA, Install etc