1. Principles and Practice of Ontology Development: Making Definitions Computable Chris Mungall LBL

2. Why make definitions computable? Doing the work all by yourself is hard, boring and error prone Automate using reasoning Bonus: – Makes the definitions easier for humans – Enables better visualization

3. Biology is modular, most ontology classes are compositional distal phalanx proximal phalanx autopod foot hand p dp pp dpf dphpph ppf pf ph (adapted from diagram by David Hill and Joel Richardson)

4. History “Cross-products” – Hill, D. P. and Blake, J. A. and Richardson, J. E. and Ringwald M: Extension and integration of the gene ontology (GO): combining GOvocabularies with external vocabularies. Genome Res 2002 Formal Concept Analysis Description Logics 1980s-present – Galen – Rector et al – GONG – Wroe, Stevens et al

5. Logical definitions Genus-differentia form – Text definition is genus-differentia form Distal phalanx of hand: – “A distal phalanx that is part of a hand.” – or “A distal phalanx[ID:2] that is part of a hand[ID:3].” – OWL: ‘distal phalanx of hand’ EquivalentTo ‘distal phalanx’ and part_of some hand – OBO-Format [Term] id: ID:1 ! distal phalanx of hand intersection_of: ID:2 ! distal phalanx intersection_of: part_of ID:3 ! hand

6. Editing logical definitions OBO-Edit – Cross-product tab Genus Differentia – Parent Editor select links to make them ‘intersections’ Protégé 4 – Equivalent Classes Enter expression

7. Using a reasoner Given: – ‘distal phalanx of hand’ EquivalentTo ‘distal phalanx’ and part_of some hand – ‘phalanx of hand’ EquivalentTo phalanx and part_of some hand – ‘distal phalanx’ is_a phalanx A reasoner can infer that: – ‘distal phalanx of hand’ is_a ‘phalanx of hand’ dp dph ph

8. Uses of a reasoner Ontology authoring – Time saving Automatically inferring is_a polyhierarchy – Quality Control detecting inconsistencies Data integration and discovery – Less applications… so far

9. Reasoners OBO-Edit – Rule Based Reasoner OWL Reasoners (Protégé 4) – Pellet – FaCT++ – HermiT

10. Difference between OBO and OWL reasoning OBO format expresses a subset of OWL – We thought this would be enough for most users – But this turned out not to be true – E.g. Lacks part – See talk later today Sufficient for basic anatomical classification

11. Modularity and external ontologies Modularity principle: – Multiple orthogonal ontologies – Use classes from O 1 as building blocks in O 2 – E.g. astrocyte differentiation anucleate cell BUT: Can pose problems for large external ontologies – CHEBI – PRO

12. Import application can choose to follow import chain – if it doesn’t, then there are dangling references the full import closure can be large! GO-BP CL imports ontology based application

13. Large Import Closure GO-BP CL ontology based application PRO CHEBI GO-CC AO

14. Bridge files BP-xp-CL BP CL basic application more advanced application current solution used by NIF, GO

15. MIREOT - Minimal Information for Retrieval of External Ontology Terms BP CL (full) CL subset copy current solution used by OBI, PRO, hemo-CL ontology author “MIREOT”s in subset of external ontology

16. Deploying cell.obo Typical User – inferred links materialized – external ontology links removed Advanced User – asserted links only – external links present – minimal external classes included

17. Ontology publishing pipeline cell_edit.obo GO/PRO/e tc subset cell_public.obo GO/PRO/e tc subset cell_basic.obo cell_edit.owl GO/PRO/e tc subset cell_public.owl GO/PRO/e tc subset cell_basic.owl reasoner filter obo2owl

18. Summary Many ontologies are seeing the benefits of using computable definitions – e.g. fly anatomy – GO slow to adopt, lots of legacy issues to work out Better to employ them from the outset – DC_CL – Hemo_CL

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