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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
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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
Outline • Heart Development – what happens? • Anatomy, Tissue, Cell, Protein • Multiscale Modelling • Pre-composition: GO, MP • Post-composition: PATO, OPB • Conclusions
Anatomy Rear View
Tissue Cardiac Jelly Endocardium Myocardium
Protein Cell Hign Delta, Low Notch Hign Notch, Low Delta
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)
<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>
Phenotype and Trait Ontology (PATO)
Human Developmental Anatomy (EHDA)
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
Ackowledgements • Randy Heiland • Maciej Swat • Lucile Houyel • Jean-Marc Schleich • Ron Summers • Fanny Bajolle • Dan Cook • John Gennari • Ryan Roper
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)
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.
CPM Model Compucell3D