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, FranceR.Summers@lboro.ac.ukhttp://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

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Heart Development: what happens?

Anatomy

Rear View

Tissue

Myocardium EndocardiumCardiac Jelly

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

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

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

Questions?

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.

CPM Model

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',))'(()),(())'(()),(( )()()1( VvSsJE vs

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Compucell3D