Software Development for Systems Biology

1. Software Development for Systems Biology Herbert M Sauro Frank Bergmann Keck Graduate Institute 535 Watson Drive Claremont, CA, 91106

2. BioSPICE/SBW – Systems Biology Workbench SBW is a lightweight framework that allows different applications written in different languages and on different platforms to communicate. Basic Simulation Capability Model Editors Broker SBML Support ?

3. Application Application SBW Broker SBW Interface SBW Interface SBW Interface Application Message Passing Architecture - Messages are passed as binary streams via TCP/IP

4. Basic Capabilities public class sbwInterface { [Help("Returns the Sine of a value")] public double Sin(double value) { return Math.Sin (value); } } - Supports a variety of data types for transmission between apps - Exception handling built-in Language and OS Independent: C/C++, Java, Delphi, .NET (C# etc.), Matlab, Perl, Python. Linux, Mac OS X, WIn32

5. Using Other Modules Module Lib File

6. Example - Matlab Building Matlab Services function y = myAdd (a, b) %SBW module SBWMath %SBW service myService %SBW method myAdd service myService sig=“double myAdd(double,double)” y = a + b Calling SBW from Matlab CLI sbwconnect; getSBML = sbwGetMethod (‘JDesigner’, ‘model’, ‘string getSBML()’); sbwStr = sbwCall (getSBML);

7. A Web Application is provided that allows every SBW Module to be wrapped up in a Web Service: Web Services from SBW/BioSPICE See www.sys-bio.org for further examples (layout, SBML validation, simulation)

8. Dynamically locate services in a given category Categories Translation SBW applications that define the translation category are capable of translating SBML into some other format (eg Matlab, XPP) and returning the translation to the caller. Analysis SBW applications that define the analysis category are capable of accepting an SBML model and doing ‘something’ with the model. Simulation SBW applications that define the simulation category mean they support the simulation API.

9. Time Course Simulation Steady State Optimization Frequency Analysis Model Editor CAD Based Model Editor Text Based Bifurcation Structural Analysis Categories permit users to ‘move’ seamlessly from one application to another taking with them the model under study User Experience Database (biomodels) ???? Stochastic Simulation

10. Examples – Model Editors JDesigner cellDesigner http://www.sys-bio.org/ http://celldesigner.org/

11. http://www.sys-bio.org/ Modeling Environment: Jarnac

12. Examples – SBML libSBML http://www.sbml.org SBW SBML

13. Examples – Simulators Oscill8 Klaus Maier C++ (Linux,Win,Mac), ODEs, Events, Emery Conrad/ Java (Linux,Win.Mac), Good Gillespie,Langevin, ODE Stuttgart Jarnac Gillespie.NET Delphi (Win), ODE, Well tested c# (Linux, Win, Mac), www.sys-bio.org www.sys-bio.org Dizzy roadRunner C# (Linux,Win.Mac), designed for SBML compliance (local and global) www,sys-bio.org Java (Linux, Win, Mac), stochastic www.isb.org

14. Specialist Modules: Bifurcation Analysis Tool The tool is used to discover whether a particular model has the potential to displa oscillatory or bistability. It uses a GA to search for specific eigenvalue patterns

15. Specialist Modules:Emery Conrad’s Oscill8 Interface Bifurcation tool begin developed at VT by Emery Conrad. By interfacing to SBW the tool can access SBML and can be run from any SBW tool.

16. Specialist Modules: Structural Analysis Tool

17. Specialist Modules: Frequency Analysis Tool; Stochastic Simulators Permits the frequency response of a model to be determined includes MCA. Permits models to be simulated using a stochastic solver. Supports additional analysis such as PDF generation, Power Spectra, autocorrelation, population metrics

18. Generic Simulation Interface Any simulator that implements the Sim API will automatically be able to use the interface via this generic simulation interface. Those API methods that are not supported in the simulator are disabled in the interface.

19. Auto layout of SBML models We use this tool to take raw SBML and generate SBML containing the layout standard that is being developed by the SBML community. Uses a spring and mass model to determine layout. Has specific rules for determining Bezier orientation and Includes a gravity field to main cohesion of disconnected sub-graphs. Anastasia Deckard

20. Non-GUI Modules • LAPACK • CVODE (ODE Solver) • NLEQ (nonlinear equation solver, f(x)=0) • Structural Analysis Algorithms • Metabolic Control Analysis and Frequency Analysis • ODE Simulators • Stochastic Simulators • libSBML • SBML Translators • Autolayout tools • Basic Optimizers of time series data to models

21. 3D Visualization of Simulation Runs Based on OpenGL, currently an installer is available for Windows but the source is portable to the Mac and Linux. Requires a decent graphics card for maximum gratification! ( http://public.kgi.edu/~fbergman )

22. 3D Visualization of Simulation Runs Based on OpenGL, currently an installer is available for Windows but the source is portable to the Mac and Linux. Requires a decent graphics card for maximum gratification! (http://public.kgi.edu/~fbergman )

23. Acknowledgments Frank Bergmann (SBW) Ravi Rao (Structural Analysis) Vijay Chickarmane (Bif Discovery Tool) Sri Paladugu (libSBML intregration) Mike Hucka and Ben Bornstein (libSBML) Alan Hindmarsh (CVODE) Nowak and Weimann (NLEQ) LAPACK (NSF/DOE) Availability: GTL www.sys-bio.org http://public.kgi.edu/~fbergman BioSPICE

24. Why Develop Software?