1. Composite Annotation for Heart Development Tariq Abdulla 1, Ryan Imms 1, Jean-Marc Schleich 2, Ron Summers 1 ICBO 2011 1.Dept Electronic & Electrical Engineering, Loughborough University, UK 2. LTSI, University of Rennes 1, France R.Summers@lboro.ac.uk http://www-staff.lboro.ac.uk/~lsrs1

2. Outline  Heart Development – what happens?  Anatomy, Tissue, Cell, Protein  Multiscale Modelling  Pre-composition: GO, MP  Post-composition: PATO, OPB  Conclusions

3. 3 Heart Development: what happens?

4. Anatomy Rear View

7. Tissue Myocardium Endocardium Cardiac Jelly

8. Protein Cell Hign Notch, Low Delta Hign Delta, Low Notch

10. 10 Multiscale Modelling

12. 12 Compucell3D and an SBML Solver BionetSolver CC3D Concentration of a subcellular species (SBML) determines cell type (CC3D) CC3D BionetSolver Cell type (CC3D) determines value for rate parameters in the subcellular model (SBML)

13. 13 0 2 […]

14. 14

15. 15 Pre-composition

16. 16 Gene Ontology

17. Mammalian Phenotype Ontology

19. 19 Post-composition

20. 20 Phenotype and Trait Ontology (PATO)

21. 21 Human Developmental Anatomy (EHDA)

22. 22 Post-composition

24. Conclusions  Gene to phenotype annotation tends to use a surgical or anatomical perspective – but does not directly include mechanism or causes  By including cell and protein level annotations, causes and mechanisms are more explicit  Post-composition enables more flexible annotation. But it is more difficult for annotators. The two strategies can be combined, but some post- composition seems necessary for multiscale and development research  In development, we can’t ignore the structure of cells  For multiple scales, there are too many combinations to pre-compose them all  Lightweight reference ontologies are more manageable, but repositories of post-composed annotations are more challenging for reasoning

25. Ackowledgements Randy Heiland Maciej Swat Lucile Houyel Jean-Marc Schleich Ron Summers Fanny Bajolle Dan Cook John Gennari Ryan Roper

26. Questions?

27. OBO intersection_of: PATO:0001163 ! decreased concentration intersection_of: inheres_in PR:000015308 ! SNAI1 intersection_of: contained_in CL:0002350 ! endocardial cell OWL EquivalentTo: PATO:0001163 and (inheres_in some PR:000015308) and (contained_in some CL:0002350)

30. 30

31. In vitro EMT WildtypeNotch1BMP2 L. Luna-zurita et al. “Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation,” The Journal of Clinical Investigation, vol. 120, 2010.

32. CPM Model Compucell3D