Tools for modeling and simulation. Pawan Dhar BII Feb 27, 2004

Transcription

1 Tools for modeling and simulation Pawan Dhar BII Feb 27, 2004

2 Modeling fundamentals revisited The why and how of modeling Qualitative vs. Quantitative Loss of information vs. Essential information Modeling complexity intuitively

3 Release date: April 2004 Dhar and Tomita: Computer simulation of the cell.

4 Release date: April 2004 Dhar and Tomita: Computer simulation of the cell.

5 Release date: April 2004 Dhar and Tomita: Computer simulation of the cell.

6 Release date: April 2004 Dhar and Tomita: Computer simulation of the cell.

7 Release date: April 2004 Dhar and Tomita: Computer simulation of the cell.

8 Release date: April 2004 Dhar and Tomita: Computer simulation of the cell.

9 GEPASI Model definition

10 GEPASI - TASKS

11 GEPASI - SCAN

12 GEPASI - TIME

13 GEPASI - OPTIMIZATION

14 GEPASI - FITTING

15 GEPASI - PLOT

16 submitted

17 Dhar et al 2004 IEEE Transactions on NanoBioscience Special issue on Systems Biology

18 Dhar et al 2004 IEEE Transactions on NanoBioscience Special issue on Systems Biology

19 Dhar et al 2004 IEEE Transactions on NanoBioscience Special issue on Systems Biology

20 Dhar et al 2004 IEEE Transactions on NanoBioscience Special issue on Systems Biology

21 SBML (SYSTEMS BIOLOGY MARKUP LANGUAGE)

22 SBML in a Nutshell A machine-readable format for representing computational models in systems biology Domain: systems of biochemical reactions Specified using UML, but mostly intended for XML Courtesy:

23 Some Common Themes SBML is useful as a common exchange format for transferring computational biochemical reaction models between software tools It is an intermediate, common-denominator format Therefore, it may not capture everything that every tool can represent the transformation may be lossy (But: tools can add their own annotations) It is not suited for representing experimental data It is not suited for representing numerical results It is not suited to be a database format for molecular databases

24 Paper on SBML Level 1 The Systems Biology Markup Language (SBML): a medium for representation and exchange of biochemical network models M. Hucka, A. Finney, H. M. Sauro, H. Bolouri, J. C. Doyle, H. Kitano, and the rest of the SBML Forum: A. P. Arkin, B. J. Bornstein, D. Bray, A. Cornish-Bowden, A. A. Cuellar, S. Dronov, E. D. Gilles, M. Ginkel, V. Gor, I. I. Goryanin, W. J. Hedley, T. C. Hodgman, J.-H. Hofmeyr, P. J. Hunter, N. S. Juty, J. L. Kasberger, A. Kremling, U. Kummer, N. Le Novere, L. M. Loew, D. Lucio, P. Mendes, E. Minch, E. D. Mjolsness, Y. Nakayama, M. R. Nelson, P. F. Nielsen, T. Sakurada, J. C. Schaff, B. E. Shapiro, T. S. Shimizu, H. D. Spence, J. Stelling, K. Takahashi, M. Tomita, J. Wagner and J. Wang Bioinformatics 19(4): ,

25 Some Applications of SBML (Example #1) Example scenario #1: 1. User develops a model of a biological process in an SBML editing/capture tool 2. User simulates the model in a simulation package to produce predictions about the changes in chemical species over time 3. User visualizes the results as time-series data plots ß ß ß Differential equations Stochastic systems Boolean logic Courtesy:

26 Some Applications of SBML (Example #2) Example scenario #2: 1. User searches a pathway database for metabolic pathways involving a specific protein, gets back multiple candidates SBML and wants to compare them 2. User sends the output to a pathway analysis tool

27 Application Support for SBML The BASIS, DARPA BioSPICE and IECA projects use SBML as their de facto standard model definition language Applications supporting SBML: Bio Sketch Pad BBN CellDesigner ERATO Kitano Symbiotic Systems Project Cellerator NASA JPL & University of California Irvine Cellware - Bioinformatics Institute, Singapore Cytoscape Institute for Systems Biology & MIT Gepasi Virginia Tech Jarnac Keck Graduate Institute JDesigner Keck Graduate Institute JigCell Virginia Tech NetBuilder University of Hertfordshire SigPath Mount Sinai StochSim Cambridge University Virtual Cell University of Connecticut Health Center WinSCAMP Keck Graduate Institute

28 Software Libraries for SBML libsbml (Author: Ben Bornstein) Reads/writes SBML, provides C and C++ API Small memory footprint & efficient runtime Validates input Portable: Linux, Windows, MacOS X, Solaris Supports SBML Levels 1 and 2 Other features planned Conversion between Level 1 and Level 2 Wrappers for Java, Python, Perl Output to other formats (e.g., text)

29 Software Libraries for SBML (cont.) MathSBML (Author: Bruce Shapiro) Mathematica package for reading SBML, converting model to ODEs, and solving & plotting model Can be used standalone or as an SBML reader Simple to use Currently supports SBML Level 1 (Level 2 coming)

30 MathSBML

31 SBML Status Published in March, 2001: SBML Level 1 version 1 Intentionally kept simple for maximum compatibility SBML Level 1 version 2 defined based on feedback Paper: Hucka et al., Bioinformatics 19(4): , 2003 SBML Level 2 currently in final draft Future: Level 3 Model composition Diagrammatic layout Multistate complex species Arrays Spatial geometry

32 FUTURE DIRECTIONS IN MODELING What does the community need? Large scale vs. smaller scale Data -> Information -> Knowledge

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34 Demo - Cellware Serial and grid versions