The Future of Disease Ontology

1. The Future of Disease Ontology • Barry Smith • Department of Philosophy, University at Buffalo • National Center for Biomedical Ontology • http://ontology.buffalo.edu/smith

2. Colors form a continuum

3. colors form a prototyped continuum

4. strategy of low hanging fruitfocus on the foci(cross-cultural, lexicalized)

5. Strategies for creating ontologies and terminologies • Ad hoc creation by each clinical or research community (à la UMLS) • versus • Coordinated creation of high quality reference ontologies in ways which serve reusability of clinical data and interoperability of with basic science • Ontologies as common railway gauge

6. A simple rule • Use singular nouns • Disease • Diseases • Disorder • Disorders • disorder • disease • disorders • diseases

7. Which strategy is more future proof? • Assumption: As time goes by the molecular/cellular basis of diseases will play an ever more important role in clinical medicine

8. OBO Foundry • A subset of OBO ontologies whose developers agree in advance to accept a common set of principles designed to assure interoperability with basic science and support for logic-based reasoning • http://obofoundry.org

9. OBO Foundry • Gene Ontology • Cell Ontology • Sequence Ontology • RNA Ontology • PATO Phenotype Ontology • OBI Ontology of Biomedical Investigations (née FuGO Functional Genomics Investigation Ontology) • FMA • RO Relation Ontology

10. GO’s three ontologies continuant occurrent biological process cellular component molecular function

11. Building out fron the original GO

12. The ontology is open and available to be used by all. • The developers of the ontology agree in advance to collaborate with developers of other OBO Foundry ontology where domains overlap. • The ontology is in, or can be instantiated in, a common formal language. • The ontology possesses a unique identifier space within OBO. • The ontology provider has procedures for identifying distinct successive versions.

13. The ontology has a clearly specified and clearly delineated content. • The ontology includes textual definitions for all terms. • The ontology is well-documented. • The ontology has a plurality of independent users. • The ontology uses relations which are unambiguously defined following the pattern of definitions laid down in the OBO Relation Ontology.

14. ORTHOGONALITY • The developers commit to working with other Foundry members to ensure community convergence on a single controlled vocabulary for each domain. • REASON: if we annotate a database or body of literature with one high-quality biomedical ontology, we should be able to add annotations from a second such ontology without conflicts • INTEGRATION PRESUPPOSES ADDITIVITY

16. Goal: when we annotate disease-related data • the disease terms we use should yield annotations which are logically consistent with – and even inferable from – other annotations using other OBO Foundry ontologies

17. Foundational Model of Anatomy (FMA) • ontology of structuralhuman anatomy

18. FMA • organized in a graph-theoretical structure involving two sorts of links or edges: • is-a(= is a subtype of ) • (pleural sac is-a serous sac) • part-of • (cervical vertebra part-of vertebral column)

19. Organ Part Organ Subdivision Anatomical Space Anatomical Structure Organ Cavity Subdivision Organ Cavity Organ Organ Component Serous Sac Tissue Serous Sac Cavity Subdivision Serous Sac Cavity is_a Pleural Sac Pleura(Wall of Sac) Pleural Cavity part_of Parietal Pleura Visceral Pleura Interlobar recess Mediastinal Pleura Mesothelium of Pleura

20. FMA follows formal rules for Aristotelian definitions • When A is_a B, the definition of ‘A ’ takes the form: • an A =Def. a B which C s... • a human being =Def. an animal which is rational

21. Example • Cell =Def. an anatomical structure which consists ofcytoplasmsurrounded by a plasma membrane

22. at every level of granularity

23. The Gene Ontology • Cross-Species • Cross-Granularity • Impressive policies for maintenance • Has initiated logic-based reforms: • relations to other ontologies • relations among GO’s 3 ontologies • Aristotelian definitions • enhanced treatment of granularity

24. Multiple Inheritance • thing • car • blue thing is_a is_a • blue car

25. Multiple Inheritance • thing • blue thing • car is_a1 is_a2 • blue car

26. is_a Overloading • Reasoning across ontologies demands that ontological relations (is_a, part_of, ...) have the same meanings in the different ontologies to be aligned.

27. Multiple Inheritance • thing • color is_a is_a • car • blue is_a • car #2947 is blue • dark blue

28. Multiple Inheritance • fracture • anatomical structure is_a is_a • limb • spiral fracture is_a • leg #29 has fracture #12 • leg

29. Multiple Inheritance • pharyngitis • anatomical structure is_a is_a • heterogeneous cluster • infectious pharyngitis is_a • disease instance #12 inheres in pharynx #29 • pharynx

30. Multiple Inheritance • is a source of errors • results are hard to maintain • serves as obstacle to integration with neighboring ontologies • hampers formulation of coherent definitions • contravenes orthogonality • no coherently defined levels

31. Multiple Inheritance • can be easily dispensed with via normalization ???

32. DO

33. DO

34. OBO Relation Ontology

35. Three fundamental dichotomies • types vs. instances • continuants vs. occurrents • dependent vs. independent

36. Three fundamental dichotomies • types vs. instances • continuants vs. occurrents • dependent vs. independent

37. Glossary • Instance: A particular entity in spatio-temporal reality. • Type: A general kind instantiated by an open-ended totality of instances which share certain qualities and propensities in common of the sort that can be documented in scientific literature

38. Glossary • Biological process instance: A change or complex of changes on the level of granularity of the cell or organism, mediated by one or more gene products. • Biological process type: A type of biological process instance.

39. Glossary • Cellular component instance: A part of a cell, including cellular structures, macromolecular complexes and spatial locations identified in relation to the cell • Cellular component type: A type of cellular component.

40. Glossary • Molecular function instance: The propensity of a gene product instance to perform actions, such as catalysis or binding, on the molecular level of granularity. • Molecular function type: A type of molecular function instance (type of propensity)

41. SCIENCE TEXTS AREREPRESENTATIONS OF TYPES IN REALITY= of what is general in reality

42. CLINICAL GUIDELINES ARE REPRESENTATIONS OF TYPES IN REALITY • diseases, therapies, diagnostic procedures (measurements) are generals, with particular instances

43. ONTOLOGIES AREREPRESENTATIONS OF TYPES IN REALITYaka kinds, universals, categories, species, genera, ...

44. substance organism animal cat instances siamese types mammal frog

45. two kinds of parthood • between instances: • Mary’s heart part_of Mary • this nucleus part_of this cell • between types • human heart part_of human • cell nucleus part_of cell • “Relations in Biomedical Ontologies”, Genome Biology, Apr 2005

46. Three fundamental dichotomies • types vs. instances • continuants vs. occurrents • dependent vs. independent

47. Continuants (aka endurants) • have continuous existence in time • preserve their identity through change • exist in toto whenever they exist at all • Occurrents (aka processes) • have temporal parts • unfold themselves in successive phases • exist only in their phases

48. You are a continuant • Your life is an occurrent • You are 3-dimensional • Your life is 4-dimensional

49. Three fundamental dichotomies • types vs. instances • continuants vs. occurrents • dependent vs. independent

50. Dependent entities • require independent continuants as their bearers • There is no grin without a cat • There is no run without a runner • There is no pumping without a pump • There is no kiss without a kisser and a kissee