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Insights into Heart Development through Composite Annotation

Explore heart development through anatomical, cellular, and protein perspectives aided by multiscale modeling and composite annotations. Learn how post-composition enhances the understanding of causes and mechanisms. This study delves into Gene Ontology, Mammalian Phenotype Ontology, and more.

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Insights into Heart Development through Composite Annotation

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  1. Composite Annotation for Heart Development Tariq Abdulla1, Ryan Imms1, Jean-Marc Schleich2, Ron Summers1 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. Heart Development: what happens?

  4. Anatomy Rear View

  5. Tissue Cardiac Jelly Endocardium Myocardium

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

  7. Multiscale Modelling

  8. 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)

  9. <Plugin Name="CellType"> <CellTypeTypeName="Medium" TypeId="0"/> <CellTypeTypeName="EndocardiumNotch" TypeId="1" /> <!--CellTypeTypeName="Mesenchymal" TypeId="2" /--> <CellTypeTypeName="CardiacJelly" TypeId="2" /> </Plugin> <Plugin Name="Contact"> <Energy Type1="Medium" Type2="Medium">0</Energy> <Energy Type1="EndocardiumNotch" Type2="EndocardiumNotch">2</Energy> […] </Plugin>

  10. Pre-composition

  11. Gene Ontology

  12. Mammalian Phenotype Ontology

  13. Post-composition

  14. Phenotype and Trait Ontology (PATO)

  15. Human Developmental Anatomy (EHDA)

  16. Post-composition

  17. 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

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

  19. Questions?

  20. 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)

  21. In vitro EMT Wildtype Notch1 BMP2 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.

  22. CPM Model Compucell3D

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