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Application of OBO Foundry Principles in GO

Application of OBO Foundry Principles in GO. Chris Mungall Lawrence Berkeley Labs NCBO GO Consortium. The GO is 3 ontologies. Molecular function (MF) Biological Process (BP) Cellular component (CC). The GO is 3 orthogonal ontologies. Molecular function

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Application of OBO Foundry Principles in GO

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  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) X oncogenesis fin regeneration acquisition of nutrients from host yes yes

  5. The GO is 3 orthogonalcanonicalspecies-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

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

  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 serine family amino acid (ChEBI) metabolism (GO) biosynthesis (GO) cysteine (ChEBI) cysteine biosynthesis (GO) Genus: biosynthesis Differentia:has_outcome cysteine computable genus-differentia definition

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

  20. 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

  21. 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

  22. Examples • GO Biological Process x OBO Cell • neuronmigration • cone cell fate specification • T cellhomeostasis • erythroctedegranulation • OBO Cell is species-neutral

  23. 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!)

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

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

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