Medical Ontologies: An Overview

1. Medical Ontologies: An Overview Barry Smith http://ifomis.de January 2004

2. IFOMIS • Institute for Formal Ontology and • Medical Information Science • Faculty of Medicine • University of Leipzig http:// ifomis.de

3. Partners • Laboratory for Applied Ontology, Trento and Rome • Language & Computing nv, Zonnegem, Belgium • Ontology Works, Baltimore • Structural Informatics Group, Department of Biological Structure, University of Washington, Seattle, USA • Cognitive Science Laboratory, Princeton University http:// ifomis.de

4. Three levels of ontology • formal (top-level) ontology dealing with categories employed in every domain: • object, event, whole, part, instance, class • 2) domain ontology, applies top-level system to a particular domain • cell, gene, drug, disease, therapy • 3) terminology-based ontology • large, lower-level system • Dupuytren’s disease of palm, nodules with no contracture http:// ifomis.de

5. Three levels of ontology • formal (top-level) ontology dealing with categories employed in every domain: • object, event, whole, part, instance, class • 2) domain ontology, applies top-level system to a particular domain • cell, gene, drug, disease, therapy • 3) terminology-based ontology • large, lower-level system • Dupuytren’s disease of palm, nodules with no contracture http:// ifomis.de

6. Three levels of ontology • formal (top-level) ontology dealing with categories employed in every domain: • object, event, whole, part, instance, class • 2) domain ontology, applies top-level system to a particular domain • cell, gene, drug, disease, therapy • 3) terminology-based ontology • large, lower-level system • Dupuytren’s disease of palm, nodules with no contracture http:// ifomis.de

7. IFOMIS • Institute for Formal Ontology and Medical Information Science • Leipzig • http://ifomis.de • philosophers and medical informaticians attempting to build and test a Basic Formal Ontology for applications in biomedical and related domains http:// ifomis.de

8. IFOMIS • use basic principles of philosophical ontology • for quality assurance and alignment of biomedical ontologies http:// ifomis.de

9. Compare: • pure mathematics (theories of structures such as order, set, function, mapping) employed in every domain • applied mathematics, applications of these theories = re-using the same definitions, theorems, proofs in new application domains • physical chemistry, biophysics, etc. = adding detail http:// ifomis.de

10. Three levels of ontology ????? • formal (top-level) ontology = • medical ontology has nothing like the technology of definitions, theorems and proofs provided by pure mathematics • 2) domain ontology • = UMLS Semantic Network, GALEN CORE • 3) terminology-based ontology • = UMLS, SNOMED-CT, GALEN, FMA http:// ifomis.de

11. Strategy • Part 1: Provide an overview of medical ontologies and of the top-level ontologies which they implicitly define • Part 2: Show how principles of classification and definition derived from top-level ontology can help in quality assurance of terminology-based ontologies and in ontology alignment • Part 3: The Gene Ontology • Part 4: Medical Fact Net http:// ifomis.de

12. http:// ifomis.de

13. UMLS Semantic Network • entity event • physical conceptual • object entity http:// ifomis.de

14. UMLS Semantic Network • entity event • physical conceptual • object entity http:// ifomis.de

15. conceptual entity • Organism Attribute • Finding • Idea or Concept • Occupation or Discipline • Organization • Group • Group Attribute • Intellectual Product • Language http:// ifomis.de

16. conceptual • entity • idea or concept • functional concept • body system http:// ifomis.de

17. entity • physical conceptual • object entity • idea or concept • functional concept • body system confusion of entity and concept http:// ifomis.de

18. Functional Concept: • Body system is_a Functional Concept. • but: • Concepts do not perform functions or have physical parts. http:// ifomis.de

19. This: is not a concept http:// ifomis.de

20. The Hydraulic Equation • BP = CO*PVR • arterial blood pressure is directly proportional to the product of blood flow (cardiac output, CO) and peripheral vascular resistance (PVR) http:// ifomis.de

21. Confusion of Ontology and Epistemology • blood pressure is an Organism Function, • cardiac output is a Laboratory or Test Result or Diagnostic Procedure • BP = CO*PVR thus asserts that • blood pressure is proportional either to a laboratory or test result or to a diagnostic procedure http:// ifomis.de

22. entities • independent dependent occurrents • continuants continuants (always dependent) • ORGANISMS ROLES PROCESSES • CELLS FUNCTIONS HISTORIES • MOLECULES CONDITIONS LIVES (diseases) (courses of • diseases) http:// ifomis.de

23. entities • independent dependent occurrents • continuants continuants (always dependent) • ORGANISMS ROLES PROCESSES • CELLS FUNCTIONS HISTORIES • MOLECULES CONDITIONS LIVES (diseases) (courses of • diseases) classes instances http:// ifomis.de

24. A three-category ontology along these lines accepted by • DOLCE = first module of Semantic Web Wonderweb Foundational Ontologies Library • BFO = IFOMIS Basic Formal Ontology • L&C LinKBase • UMLS-SN • Gene Ontology http:// ifomis.de

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26. Principles for Building Medical Ontologies

27. Examples • Don’t confuse entities with concepts • Don’t confuse domain entities with logical or computational structures • Don’t confuse ontology with epistemology • Don’t confuse is_a with has_role http:// ifomis.de

28. Further Principles • univocity: terms should have the same meanings (and thus point to the same referents) on every occasion of use • UMLS-SN: • ‘organization’ = body plan • ‘organization’ = social organization http:// ifomis.de

29. univocity • Gene Ontology: • ‘part_of’ = ‘can be part of’ (flagellum part_of cell) • ‘part_of’ = ‘is sometimes part of’ (replication fork part_of the nucleoplasm) • ‘part_of’ = ‘is included as a sublist in’ http:// ifomis.de

30. don’t forget instances • part_of as a relation between classes • vs. partas a relation between instances • A part_of B • every instance of A is part of some instance of B • every instance of B has some instance of A as part http:// ifomis.de

31. Part_of as a relation between classes is more problematic than is standardly supposed • testis part_of human being ? • heart part_of human being ? http:// ifomis.de

32. objectivity • which classes exist is not a function of our biological knowledge. • (Terms such as ‘unknown’ or ‘unclassified’ or ‘unlocalized’ do not designate biological natural kinds.) • GO: • aminoadipate-semialdehyde dehydrogenase complex is_a unlocalized http:// ifomis.de

33. rules for definitions • intelligibility: the terms used in a definition should be simpler (more intelligible) than the term to be defined • definitions: do not confuse definitions with the communication of new knowledge http:// ifomis.de

34. substitutability • in all so-called extensional contexts a defined term should be substitutable by its definition in such a way that the result is both grammatically correct and has the same truth-value as the sentence with which we begin • GO:0015070: toxin activity • Definition: Acts as to cause injury to other living organisms. http:// ifomis.de

35. substitutability • There is toxin activity here • There is acts as to cause injury to other living organisms here http:// ifomis.de

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37. GO: the Gene Ontology • 3 large telephone directories of standardized designations for gene functions and products • organized into hierarchies via is_a and part_of http:// ifomis.de

38. GO • can in practice be used only by trained biologists(withknow how) • whether a GO-term truly stands in the is_a relation depends e.g. on the type of organism involved • glycosome is part-of cytoplasm only for Kinetoplastidae • Computers have no counterpart of such context-dependent know-how http:// ifomis.de

39. GO divided into three disjoint term hierarchies • the cellular component ontology, • e.g. flagellum, chromosome, cell • the molecular function ontology, • e.g. ice nucleation, binding, protein stabilization • the biological process ontology, • e.g. glycolysis, death http:// ifomis.de

40. Primary aim of GO not rigorous definition and principled classification but rather: providing a practically useful framework for keeping track of the biological annotations that are applied to gene products http:// ifomis.de

41. Thesis 1 • With increasing size, GO will be required to increase the degree to which it is a controlled vocabulary which satisfies not merely the needs of human biologists but also the needs of automatic consistency-checking and updating systems http:// ifomis.de

42. Thesis 2 • GO can realize its goal more adequately (and avoid many coding errors) by taking ontology (especially the logic of classifications and definitions) seriously http:// ifomis.de

43. GO: the Gene Ontology • GO divided into 3 separate hierarchies each organized via is_a and part_of http:// ifomis.de

44. Problems with is_a • A is_a B = every instance of A is an instance of B http:// ifomis.de

45. Problems with is_a • Holliday junction helicase complex is_a • unlocalized • protein storage vacuole is_a • vacuole (sensu Streptophyta) • R7 differentiation is_a eye photoreceptor differentiation (sensu Drosophilia). http:// ifomis.de

46. Uses of part_of • – membrane part-of cell, intended to mean “a membrane is a part-of any cell” • – flagellum part-of cell, intended to mean “a flagellum is part-of some cells” • – replication fork part-of cell cycle, intended to mean: “a replication fork is part-of the nucleoplasm only during certain times of the cell cycle” • – regulation of sleep part-of sleep, should be corrected to: “regulation of sleep is co-located with and is causally involved with the sleep process”. http:// ifomis.de

47. Problems with part_of • ‘part_of’ = ‘can be part of’ (flagellum part_of cell) • ‘part_of’ = ‘is sometimes part of’ (replication fork part_of the nucleoplasm) • ‘part_of’ = ‘is included as a sublist in’ http:// ifomis.de

48. Problem’s with GO Molecular Functions • anti-coagulant activity (defined as: “a substance that retards or prevents coagulation”) • enzyme activity (defined as: “a substance that catalyzes”) • structural molecule (defined as: “the action of a molecule that contributes to structural integrity”) http:// ifomis.de

49. GO:0005199: structural constituent of cell wall • Definition: The action of a molecule that contributes to the structural integrity of a cell wall. • confuses actions, which GO includes in its function ontology, with constituents, which GO includes in its cellular component ontology http:// ifomis.de

50. extracellular matrix structural constituent + • puparial glue (sensu Diptera) • structural constituent of bone • structural constituent of chorion (sensu Insecta) • structural constituent of chromatin • structural constituent of cuticle + • structural constituent of cytoskeleton • structural constituent of epidermis + • structural constituent of eye lens • structural constituent of muscle • structural constituent of myelin sheath • structural constituent of nuclear pore • structural constituent of peritrophic membrane (sensu Insecta) • structural constituent of ribosome • structural constituent of tooth enamel • structural constituent of vitelline membrane (sensu Insecta) http:// ifomis.de