Composite Annotation for Heart Development
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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, UK2. LTSI, University of Rennes 1, [email protected]://www-staff.lboro.ac.uk/~lsrs1
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Outline
Heart Development – what happens? Anatomy, Tissue, Cell, Protein
Multiscale Modelling Pre-composition: GO, MP Post-composition: PATO, OPB Conclusions
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Heart Development: what happens?
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Anatomy
Rear View
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Tissue
Myocardium EndocardiumCardiac Jelly
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ProteinCell
Hign Notch,Low Delta
Hign Delta,Low Notch
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Multiscale Modelling
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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)
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<Plugin Name="CellType"> <CellType TypeName="Medium" TypeId="0"/> <CellType TypeName="EndocardiumNotch" TypeId="1" /> <!--CellType TypeName="Mesenchymal" TypeId="2" /--> <CellType TypeName="CardiacJelly" TypeId="2" /> </Plugin>
<Plugin Name="Contact"> <Energy Type1="Medium"
Type2="Medium">0</Energy> <Energy
Type1="EndocardiumNotch" Type2="EndocardiumNotch">2</Energy>[…]</Plugin>
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Pre-composition
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Gene Ontology
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Mammalian Phenotype Ontology
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Post-composition
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Phenotype and Trait Ontology (PATO)
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Human Developmental Anatomy(EHDA)
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Post-composition
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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
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Ackowledgements
•Randy Heiland•Maciej Swat•Lucile Houyel•Jean-Marc Schleich•Ron Summers•Fanny Bajolle•Dan Cook•John Gennari•Ryan Roper
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Questions?
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OBO intersection_of: PATO:0001163 ! decreased concentration intersection_of: inheres_in PR:000015308 ! SNAI1 intersection_of: contained_in CL:0002350 ! endocardial cell
OWLEquivalentTo: PATO:0001163 and (inheres_in some PR:000015308) and (contained_in some CL:0002350)
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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.
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CPM Model
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',))'(()),(())'(()),(( )()()1( VvSsJE vs
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Compucell3D
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