1. Application of OBO Foundry Principles in GO Chris Mungall Lawrence Berkeley Labs NCBO GO Consortium

2. The GO is 3 ontologies Molecular function (MF) Biological Process (BP) Cellular component (CC)

3. The GO is 3 orthogonal ontologies Molecular function –(a kind of dependent continuant) Biological Process –(a kind of occurrent) Cellular component –(a kind of independent continuant)

4. The GO is 3 orthogonal ontologies of canonical biology Molecular function –(a kind of dependent continuant) Biological Process –(a kind of occurrent) Cellular component –(a kind of independent continuant) oncogenesis X fin regeneration yes acquisition of nutrients from host yes

5. The GO is 3 orthogonal canonical species-neutral ontologies Molecular function –many core functions Biological Process –core shared processes ( e.g. transcription) –processes specific to organism types ( e.g. fin development, fly courtship behaviour) Cellular component –prokaryotes and eukaryotes

6. part of the part_of tree in GO

7. Granularity of the GO FunctionProcessContinuant MolecularGO-MF GO-BPGO-CC (Sub?)Cellul ar GO-BPGO-CC OrganismalGO-BP

8. The GO is an ontology, with rich terminological features GO ‘terms’ are actually representations of types (aka kinds, universals, classes) –The actual terms (i.e. the phrases used by biologists) are attached to the representations of types as names and synonyms synonyms have linguistic relations to the GO types –exact, broad, narrow, related distinct from ontological relations between GO types –is_a, part_of GO is moving to genus-differentia style definitions –Many definitions are still dictionary-style, terminological describe how the term is used

9. Genus differentia definitions central nervous system morphogenesis Genus: morphogenesis Differentia: has_outcome central nervous system The process by which the anatomical structure of the central nervous system is generated and organized

10. The GO is both reference and application ontology The same artefact (i.e. file) is used for both ontology editing and data annotation This has worked reasonably well until now We may encourage making a distinction –application views (aka GO slims) currently only used to present a very small subset of GO consider wider use for extracting most of ontology

11. Relations in GO (current) part_of –conforms to RO X part_of Y: all Xs are part_of some Y (for the entirety of the duration of the existence of the X) –e.g. nucleus part_of cell (all nuclei are always part_of a cell, not all cells have a nucleus as part) for both continuants and processes –no ordering for processes is_a –sort-of conforms to RO X is_a Y: all Xs are Ys (for the entirety of Xs existence) but there are issues with is_a in GO: –is_a incompleteness –is_a polyhierarchies

12. is a has issues Not all GO types have is_a parents –not a problem in MF –fixed in CC (July 2006) –being fixed in BP (Sept 2006: right now, here in Seattle) Still a contentious issue? –is_a completion requires new high-level types in ontology –perceived as being too abstract by biologists –simple solution: application ontology remove high level terms in annotation view

13. is_a polyhierarchies is_a diamonds cause problems –tangled DAGs, easy to make mistakes Source of problems typically due to multiple axes of classification –e.g. due to composite terms Solution: –Genus - differentia (aristotelian) definitions aka cross-products [Hill et al] –Always a single genus choose consistent axis of classification –Allow classifier/reasoner to provide different views of ontology

14. a tangled hierarchy in GO problem: mixes (at least) two axes of classification

15. biosynthesis is_a metabolism

16. cysteine is_a serine family amino acid is_a amino acid is_a amine

17. cysteine is_a serine family amino acid is_a amino acid is_a serine

18. The solution: separate the axes cysteine biosynthesis (GO) Genus: biosynthesis Differentia: has_outcome cysteine biosynthesis (GO) metabolism (GO) cysteine (ChEBI) serine family amino acid (ChEBI) computable genus-differentia definition

19. Compute the subsumption DAG from the definition cysteine biosynthesis (GO) Genus: biosynthesis Differentia: has_outcome cysteine cysteine metabolism (GO) serine family amino acid biosynthesis (GO) the DAG is required for applications such as annotation search

21. Pre- and post- composition References to types can be pre-composed in ontology, prior to annotation –Ontology editor creates term, with ID –Use reasoners to classify the DAG automatically References to types can be post-composed (created on the fly) at annotation time –No term with ID is created Computationally, it makes no difference –provided we adhere to the genus-differentia formalism

22. OBO Foundry practices and pre-composition Pre-composition of terms in the ontology is good as it creates a map of biological reality, linking foundry ontologies –within reason

23. Examples GO Biological Process x OBO Cell –neuron migration –cone cell fate specification –T cell homeostasis –erythrocte degranulation OBO Cell is species-neutral

24. Current status The ability to effectively created computationally visible genus-differentia definitions is new to most OBO ontologies Soon to be created: –SO (many terms now done) –GO-BP definitions referencing OBO-Cell –OBO Disease definitions referencing FMA –And more… Difficult: –GO-BP and ChEBI (chemical entities) –GO-BP and anatomy (we need CARO!)

25. development in GO (current) neural tube formation neural tube development neural plate formation neural plate development GO part_of neural plate morphogenesis (is_a not shown)

26. development in GO (future) presumptive spinal cord neural plate neural keel neural rod neural tube spinal cord transformation_of neural tube formation neural tube development neural plate formation neural plate development has_participant AO GO part_of neural tube formation Genus: tube formation Differentia: has_outcome neural tube neural plate morphogenesis