1. Metamodeling and Modeling language for Systems Biology SB-UML Magali ROUX-ROUQUIE CNRS, Paris

2. What is Systems Biology ? T. Ideker, T. Galitski, L. Hood. A new approach to decoding life: Systems biology. Annu. Rev. Genomics Hum Genet 2 (2001) 343-372.

3. DATA level 1 DATA MODEL level 2 Virtual Cell Relational Model Object Model SBML (XML) file Ontology http://franck.fleurey.free.fr/NeuralNetwork/Uml_diagram.htm

4. DATA level 1 DATA MODEL level 2 METAMODEL level 3 META METAMODEL level 4 Virtual Data Relational Model Object Model SBML (XML) file Ontology http://franck.fleurey.free.fr/NeuralNetwork/Uml_diagram.htm Language

5. METAMODELlevel MODEL level BIND database model Action ontology model ? Metamodel for Systems Biology

6. Looking for a Conceptual Metamodel … Static Dynamic

7. Mapping between State Description and Process Description M. Roux-Rouquie and JL Le Moigne. The systemic paradigm and its relevance for modeling biological functions (2002) CR Biol. 325: 419-430.

8. Looking for a modeling language: The Unified Modeling Language (1) UML is a language originally developed for software engineering. This is a language for visualizing, specifying, constructing and documenting any kind of systems. It decouples the model from the platform. It describes: –concepts and their relationships (abstract syntax and semantics) –constraint language (OCL) –diagrams and notation for concepts –interchange format (XMI)

9. Major Advantages A standard language maintained by OMG and used by thousands of people over the world, Both, the formalism and the knowledge can be represented in UML Different formalisms can be expressed in the same standardized language Looking for a modeling language: The Unified Modeling Language (2)

10. The Unified Modeling Language (UML) State diagramInteraction diagram UML State diagram and Interaction Diagram

11. Extensions for RT systems with UML 2.0 (IBM Rational) Passive classActive class

12. A SB profile with UML 2.0 (CNRS proposal against RPF14) OMGOMG Life SciencesLife Sciences Research DTFResearch DTF MeetingMeeting Boston, September 9th 2003

13. SB-UML: FormOccurrence © CNRS

14. Example: TR_Photo-Isomerization Definition: Modifications of the molecular geometry after the absorption of a photon.

15. Molecular State vs population

16. Modeling Simulation

17. CellML vs SB-UML

18. Modeling States of cyclin-dependent Cdk2 kinase

20. Individual cell vs population Signal (molecule concentration) per cell In a imited population (less than 10 cells) In a large population

21. Conclusion (1) Model-driven approach Metamodel for systems biology in UML UML models in a variety of formalisms Semantic integration (before 2010, as announced by Alex Polonsky !)

22. Conclusion (2) Model transformation