Phenotype annotation using ontologies

1. Phenotype annotation using ontologies Chris Mungall (+ BS) Berkeley Bioinformatics and Ontologies Project (BBOP) National Center for Biomedical Ontology (NCBO)

2. A biological ontology is: • A precise representation of some aspect of biological reality sense organ • what kinds of things exist? eye disc is_a • what are the relationships between these things? develops from eye part_of ommatidium

3. OBD Foundry definition of a phenotype • A collection of qualities inhering in one or more entities • Examples: • the quality of being reduced mass inhering in bone (i.e osteoporosis) • the quality of being hypoplastic inhering in a midface • the quality of lacking asters inhering in spermatocytes • Qualities are real and have spatial or spatiotemporal extent

4. PATO : qualities • Purpose: • originally for annotation of mutant phenotypes • now: OBO Foundry candidate reference ontology for biological qualities • Both spatial and spatiotemporal attributes • shape (inheres in a 3D object) • rate (inheres in a process) • Multiple levels of granularity

5. Old EAV representation AO GO, CLO, … PATO PATO

6. Problems with EAV What is attribute, what is value? Every attribute is turned into a relation?

7. Towards a Single Hierarchy of Monadic Qualities • long length is_a length • hot temperature is_a temperature • cylindrical shape is_a shape • extended cylindrical shape is_a cylindrical shape ontologies are about types; values reflect a confusion between types and instances

8. New Quality Ontology CARO, GO, CL, … PATO

9. Extensions • E+Q is not enough in itself • Relational attributes • Relative attributes • Measurements • the measurement is not the phenotype

10. Relational attributes • Most qualities are monadic • they inhere in a single self-connected entity • e.g. shape, color • Some qualities are relational (instance-to-type) • they inhere in >1 entity • e.g. sensitivity, tolerance • Some qualities are relative (instance-to-instance) • e.g. taller_than • Soon PATO will indicate which qualities are relational

11. E+Q extended with secondary relata

12. Problem of Lacks • Common attributes for systematics • spermatocyte devoid of asters • Example: wingless • E=wing, A=presence, V=absent • but there is no wing for the quality of absence to inhere in • Consider instead • The thorax (or whole fly) has the quality of being wingless =def. A normal thorax of this type has_a wing but not (this instance has_a wing) lacks is like instantiation: it relates instances to types

13. Ontological relations for anatomy and phylogeny • Basic set (from OBO relations ontology) is_a part_of • ontogenic/developmental derives_from transformation_of • New relations

14. Instances and types • Dictionary definitions leave lots of room for ambiguity • especially for relations • We must be careful to distinguish between instances and types when defining relations • We directly perceive and interact with instances • As scientists we are primarily interested in types • Type level relations are defined in terms of instances

15. is_a • also known as: subtype_of • X is_a Y • given any x that instantiates X at time t, x also instantiates Y at time t • informally: all Xs are always Ys • is_a is a transitive relation • if X is_a Y and Y is_a Z then X is_a Z • Examples: • left eyeball is_a eyeball • eye development is_a organ development • monotreme is_a mammal

16. organ is_a cavitated organ is_a eyeball types instance_of instances

17. part_of • X part_of Y (where X and Y are types) • given any x that instantiates X at time t, there exists some y at time t such that y instantiates Y and x part_of y • informally: all Xs are part of some Y at all times • part_of is a transitive relation • if X part_of Y and Y part_of Z then X part_of Z • Examples: • ommatidium part_of compound eye • male genital system part_of body • placenta part_of female reproductive system

18. ontogenic relations • OBO relations ontology defines: • transformation_of (single entity, identity preserving) • derives_from (fusion and fission) • Most OBO ontologies currently use develops_from • can be considered the union of transformation_of and derives_from • Transitive • Example: • T cell develops_from T lymphoblast • male reproductive organ develops_from gonad primordium • female reproductive organ develops_from gonad primordium

19. in_organism • X in_organism Y (where X and Y are types) • given any x that instantiates X at time t, there exists some y at time t such that y instantiates Y and x part_of y • informally: all Xs are in some organism of type Y • Examples: • vertebrate eye in_organism vertebrate • placenta in_organism mammal [discuss!]

20. not_in_organism • Features are often lost • X not_in_organism Y (where X and Y are types) • given any x that instantiates X at time t, there exists no y at time t such that y instantiates Y and x part_of y • informally: no Xs are in any organism of type Y • Examples: • ceratobranchial 5 tooth not_in_organism Gonorhynchiformes • To be added to OBO relations ontology • Do we need organism_lacks? • Warning: exceptions are bad for ontologies • how to deal with return of atavistic features?

21. coelomata is_a is_a vertebrate arthropod eye in_organism in_organism is_a is_a vertebrate eye compound eye part_of ommatidium