1 VT

2 Medical Ontology Barry Smith

3 IFOMIS Institute for Formal Ontology and Medical Information Science Faculty of Medicine University of Leipzig

4 Reference Ontology An ontology is a theory of a domain of entities in the world Ontology is outside the computer seeks maximal expressiveness and adequacy to reality and sacrifices computational tractability for the sake of representational adequacy

5 Reference Ontology a theory of the tertium quid – called reality – needed to hand-callibrate database/terminology systems

6 Methodology Get ontology right first (realism; descriptive adequacy; rather powerful logic); solve tractability problems later

7 The Reference Ontology Community IFOMIS (Leipzig) Laboratories for Applied Ontology (Trento/Rome, Turin) Foundational Ontology Project (Leeds) Ontology Works (Baltimore) Ontek Corporation (Buffalo/Leeds) Language and Computing (L&C) (Belgium/Philadelphia)

8 Domains of Current Work IFOMIS Leipzig: Medicine, Bioinformatics Laboratories for Applied Ontology Trento/Rome: Ontology of Cognition/Language Turin: Law Foundational Ontology Project: Space, Physics Ontology Works: Genetics, Molecular Biology Ontek Corporation: Biological Systematics Language and Computing: Natural Language Understanding

9 Ontologie als Zweig der Philosophie die Wissenschaft von den Arten und Strukturen von Objekten, Qualitäten, Prozessen, Ereignissen, Funktionen und Relationen in allen Bereichen der Wirklichkeit

10 Aristotle Der erste Ontologe

11 Eine biologische Ontologie

12 Linné 1763: Genera Morborum (Nosologie oder Ontologie der Krankheitsarten)

13 Q: Warum Ontologie in der medizinischen Informatik? A: Das Turm von Babel-Problem der Informationssysteme

14 Turm von Babel Jedes Informationssystem basiert auf einer eigenen Terminologie Wie können wir die Inkompatibilitäten lösen, die entstehen, wenn Daten aus verschiedenen Quellen kombiniert werden? Vgl. Wie können wir Anatomie und Physiologie integrieren?

15 Wie lösen Medizinstudenten dieses Problem? Vielfach erst durch die Begegnung mit dem Patienten Der Patient und die in ihm ablaufenden Prozesse dienen als Kristallisationspunkt für eine sinnvolle Ordnung sonst isoliert stehender (gelernter) Fakten. (Aus Wissen-dass wird Wissen-wie)

16 Dem Computer fehlt praktisches Wissen Wie können in Medizininformations- systemen isolierte Datenartefakte zu konsistentem und anwendbarem Wissen integriert werden?

17 Ursprünglicher Traum der Ontologie in der Informatik Eine einzige allumfassende Taxonomie aller Gegenstandsarten, die als zentrales integrierendes Kategoriensystem für alle Informationssysteme dient. Dieser Traum ist ausgeträumt...

18 Gegenwärtige Lösungen Standardisierte Terminologien UMLS SNOMED ICD-10 Gene Ontology Digital Anatomist usw.

19 Standardisierte Terminologien sollen Zugriff auf biomedizinische Literatur und Faktendatenbanken erleichtern Beispielsweise um Verbindungen zwischen spezifischen Genen und spezifischen Körperreaktionen auffindbar zu machen Eine neue Art medizinischer Forschung soll dadurch ermöglicht werden

20 Database and terminology standardization is desparately needed in medical and bioinformatics to enable the huge amounts of existing data to be fused together automatically

21 To reap the benefits of standardization we need to make ONE SYSTEM out of many different terminologies But how? Through government edict? (Scandinavia) Through efforts of international standards bodies (ISO, CEN …)? Through UMLS Metathesaurus?

22 Zentrale Schaltstelle UMLS Universal Medical Language System National Library of Medicine Bethesda, MD

23 UMLS Metathesaurus eine riesige Kombination verschiedener maschinenlesbarer Quellterminologien 800,000 Begriffe 10 Mio. Beziehungen

24 Beispiele für Quell-Terminologien SNOMED-RT S ystematized No menclature of Med icine MeSH Me dical S ubject H eadings

25 is_a trees hormone peptide hormone digestive hormone adrenocorticotropin glycopeptide hormone follicle-stimulating hormone

26 is_a = ist ein / ist von der Art Diabetes Melletus is_a Disease

27 Bad Coding deriving from over-simplification and from failure to pay attention to ontological principles Z.B. SNOMED both_testes is_a testis (beide_Hoden ist_ein Hoden)

28 Terminological Incompatibilities

29 Representation of Blood in SNOMED Blood is_a Tissue

30 Representation of Blood in MeSH Blood is_a Bodily Fluid

31 Bad Coding Incompatibilities Context-Dependence Standardized Terminologies must be used properly

32 people are lazy and idiosyncratic Sie machen Schreibfehler Jeder pflegt seine eigene Terminologie, die sich mehr oder weniger von der anderer Akteure unterscheidet Sie verwenden verschiedene natürlich- sprachliche Darstellungen der gleichen medizinischen Phänomena

33 The codes are not formulated on the basis of clear principles Therefore inconsistent Unintuitive Difficult to train people to use them Application often depends on context- dependent knowledge

34 The IFOMIS Contribution help to improve standardizations through constructive criticism based on robust ontological principles

35 UMLS Metathesaurus eine riesige Kombination verschiedener maschinenlesbarer Quellterminologien Semantic Network UMLS Semantic Network Semantic Types bestehend aus 134 Semantic Types soll Ordnung in diesem Wust schaffen

36 UMLS Semantic Network entity event physical conceptual entity entity

37 conceptual entity Organism Attribute Finding Idea or Concept Occupation or Discipline Organization Group Group Attribute Intellectual Product Language

38 conceptual entity Organism Attribute Finding Idea or Concept Occupation or Discipline Organization Group Group Attribute Intellectual Product Language

39 Idea or Concept Functional Concept Qualitative Concept Quantitative Concept Spatial Concept Body Location or Region Body Space or Junction Geographic Area Molecular Sequence Amino Acid Sequence Carbohydrate Sequence Nucleotide Sequence

40 INNSBRUCK is an Idea or Concept

41 Idea or Concept Functional Concept Qualitative Concept Quantitative Concept Spatial Concept Body Location or Region Body Space or Junction Geographic Area Molecular Sequence Amino Acid Sequence Carbohydrate Sequence Nucleotide Sequence

42 Confusion of Ontology and Epistemology Physical Entity Chemical Entity Chemical Viewed Structurally Functionally

43 Confusion of Ontology and Epistemology 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). Cardiac Output in UMLS = A Finding

44 UMLS-Semantic Types: 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

45 The goal Formulate clear principles for building ontologies Reconstitute the UMLS Semantic Types on the basis of these principles

46 Zusammenarbeit mit der National Library of Medicine Revision der UMLS Semantic Types und der Gene Ontology

47 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

48 GO can in practice be used only by trained biologists (with know 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

49 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

50 Definition of Molecular Function the action characteristic of a gene product. On March 2003 all nodes in the Molecular Function ontology (except the root) had activity added to their names -- confusion of function with functioning (how deal with dormant/suppressed functions?)

51 Definition of Biological Process A phenomenon marked by changes that lead to a particular result, mediated by one or more gene products

52 How are the 3 ontologies related? Function = the action characteristic of a gene product. Process = phenomenon marked by changes that lead to a particular result, mediated by one or more gene products No part-whole relations across ontologies?

53 The GO isa relation in its intended meaning indicates a necessary relationship. That is, when we say eukaryotic cell isa cell, we mean that every eukaryotic cell is a cell. Confusion of necessarily, universally, and permanently (No time in GO)

54 part_of The Relation part-of: The intended meaning of part-of as explained in the GO Usage Guide is: can be a part of, not is always a part of

55 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.

56 Need to find ways to deal with time in medical informatics Functions vs. Realizations of Functions Function is still there even when not being realized need to be clear about the distinction between continuants and occurrents

57 SNAP and SPAN

58 SNAP and SPAN Substances and processes Continuants and occurrents In preparing an inventory of reality we keep track of these two different categories of entities in two different ways

59 Substances and processes exist in time in different ways substance t i m e process

60 Need for different perspectives Not one ontology, but a multiplicity of complementary ontologies Cf. Quantum mechanics: particle vs. wave ontologies

61 SNAPshot Video (SPAN) ontology ontology substance t i m e process

62 SNAP and SPAN stocks and flows commodities and services product and process anatomy and physiology synchrony and diachrony

63 SNAP and SPAN SNAP entities - have continuous existence in time - preserve their identity through change - exist in toto if they exist at all SPAN entities - have temporal parts - unfold themselves phase by phase - exist only in their phases/stages

64 SNAP: Entities existing in toto at a time

65 Three kinds of SNAP entities Substances Dependent SNAP entities (qualities, functions, roles, powers …) Spatial regions, Contexts, Niches

66 Functions The function of the heart is to pump blood

67

68 SNAP Fiat part of substance Extremity (hand, arm) Bodily System

69 SPAN: Entities extended in time

70 SPAN: Entities extended in time

71 SPAN: Entities extended in time Functioning The hearts pumping of blood

72 Granularity spatial regionsubstance parts of substances are always substances

73 Granularity spatial regionsubstance parts of spatial regions are always spatial regions

74 Granularity process parts of processes are always processes

75 MORAL Relations crossing the SNAP/SPAN border are never part-relations

76 Relations crossing the SNAP/SPAN border are never part-relations Johns life substance John physiological processes sustaining in existence

77 DIGESTIVE SYSTEM

78 RESPIRATORY SYSTEM

79 URINARY SYSTEM

80 IMMUNE SYSTEM

81 CIRCULATORY SYSTEM

82 CIRCULATORY SYSTEM (Principal Organs)

83 The autonomous part of the nervous system (regulatory links to other systems)

84 ENDOCRINE SYSTEM

85 Bodily Systems are Component Parts of Bodies respiratorydigestive skeletal circulatory musculatory immune

86

87 A system for keeping your jewels safe

88 Bodily Systems interconnect

89 Systems are SNAP entities They are dependent continuants We can take photographs of them

90 The Monarchic System of Government