ifomis.org Ontologie-basierte Qualitätssicherung medizinischer Terminologien Barry Smith with thanks to Werner Ceusters, Anand Kumar and Cornelius Rosse

ifomis.org Problems with UMLS Each is a ‘fusion’ of several source vocabularies, some of dubious quality They were fused without an ontological system being established first They contain circularities, taxonomic gaps, and unnatural ad hoc determinations They are representations of concepts, not of reality

ifomis.org UMLS Metathesaurus traps

ifomis.org Problem: Confusion of concepts and entities in reality

ifomis.org Blood Pressure Ontology The hydraulic equation: BP = CO*PVR arterial blood pressure (BP) is directly proportional to the product of blood flow (cardiac output, CO) and peripheral vascular resistance (PVR).

ifomis.org UMLS-Semantic Types: blood pressure is an Organism Function, cardiac output is a Laboratory or Test Result or Diagnostic Procedure

ifomis.org UMLS-Semantic Types: BP = CO*PVR thus asserts that blood pressure is proportional either to a laboratory or test result or to a diagnostic procedure

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SNOMED-CT 900,000 ‘concepts’ Description Logic infrastructure NIH + NHS gesegnet College of American Pathologists SNODENT

ifomis.org Confused treatment of is_a and part_of beide_Hoden is_a Hoden beide_ Gebärmuttern is_a Gebärmutter teilweise_Entfernung_der_Blase is_a Entfernung_ der_Blase.

ifomis.org Confused treatment of is_a and part_of Halbextraktion_aus_Steißlage is_a Extraktion_aus_Steißlage Extraktion_aus_Steißlage is_a vollständige_Steißgeburt ____________________________ Halbextraktion_aus_Steißlage is_a vollständige_Steißgeburt

ifomis.org Confused treatment of objects and processes diagnostische_endoskopische_Untersuchung _eines_Mediastinums_NOS is_a Mediastinoskop.

ifomis.org Confusion of object with knowledge about object Kontrazeption is_a funktionaler_Befund

ifomis.org Just plain confusion labial vein is_a vein of head labial vein is_a vulval vein Dupuytren-Krankheit,_ Knoten_ohne_Kontraktur is_a Kontraktur_der_Palmarfaszie

ifomis.org Problems with logical combination ‘Veterinary proprietary drug AND/OR biological’ * Such terms not designate natural kinds. (Which biological classes exist is not a matter of logical combination of terms or concepts) *has 2532 children in SNOMED-CT

ifomis.org Confusion of part_of and overlaps_with Struktur_des_Nervus_tibialis is_a Oberschenkelteil Struktur_des_Nervus_tibialis is_a Unterschenkelstruktur

ifomis.org Missed subsumption detection Missing: is_a neoplasm of heart

ifomis.org Are these just isolated examples of errors?

ifomis.org Why Description Logics are not enough SNOMED-RT amputation of toe is_a amputation of foot Hahn-Schulz improvements re part-of in SNOMED-CT

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National Cancer Institute caCORE Cancer Informatics Infrastructure Backbone caBIO Cancer Bioinformatics Infrastructure Objects: Biomedical objects to facilitate the communication and integration of information from the various initiatives supported by the NCICB

ifomis.org caBIO architecture Connectivity at programming interface level

ifomis.org Instead of building an ontology of cancer the NCI builds an ontology (or a ‘model’) of the data in the NCI’s own computers

ifomis.org NCI Thesaurus a biomedical thesaurus created specifically to meet the needs of the NCI semantically modeled cancer-related terminology built using Description Logic

ifomis.org Search for “cancer”

ifomis.org Missed subsumption detection

ifomis.org Recall SNOMED confusion of ‘part’ and ‘structure’ Struktur_des_Nervus_tibialis is_a Oberschenkelteil Struktur_des_Nervus_tibialis is_a Unterschenkelstruktur

ifomis.org Confusion of ‘part’ and ‘structure’ and ‘system’ and ‘substance’

ifomis.org NCI Thesaurus Root concepts Anatomic Structure, Anatomic System, or Anatomic Substance ? Or ? Does the NCI not know to which category Any item classified there belongs ? Anatomic Substance ? If yes, why is gene product not subsumed by it ? If no, why are drugs and chemicals not subsumed by it ?

ifomis.org Conceptual entity Definition: none Semantic type: – Conceptual entity – Classification Subconcepts: – Action: definition: action; a thing done – And: Definition: an article which expresses the relation of connection or addition, used to conjoin a word with a word,...

ifomis.org Action is_a Conceptual Entity And is_a Conceptual Entity Swimming is healthy and contains 8 letters Conceptual entity

ifomis.org Definition of “cancer gene”

ifomis.org NCI Thesaurus architecture Disease BreastBreast neoplasm Disease-has-associated-anatomy ISA Findings-And- Disorders-Kind Anatomy-Kind “Formal subsumption” or “inheritance” “Associative” relationships providing “differentiae” “Kinds” restrict the domain and range of associative relationships What diseases have a diameter of over 3 cm ?

ifomis.org Confusion of objects and the states in which they participate Disease BreastBreast neoplasm Disease-has-associated-anatomy ISA Findings-And- Disorders-Kind Anatomy-Kind

ifomis.org Cancer Data Standards Repository (caDSR) “One of the problems confronting the biomedical data management community is the panoply of ways that similar or identical concepts are described.” The real problem is that concepts are being described.

ifomis.org Problems with the concept orientation Ad hoc readings of statements of the type C1- relationship-C2 – California is-part-of United States // California isa name Concepts do not necessarily correspond to anything in reality: sorcerer, unicorn, leprechaun,... Language can make strings of words look as if it were terms – Middle lobe of left lung

ifomis.org “Ontology” In information science: – An ontology is a description (like a formal specification of a program) of the concepts and relationships that can exist for an agent or a community of agents. In philosophy: – Ontology is the science of what is, of the kinds and structures of objects, properties, events, processes and relations in every area of reality.

ifomis.org Why are concepts not enough? – only by looking at referents in reality can we work out how the concepts used by different communities relate to each other

ifomis.org Ontology as Bridge for Understanding Cancer Information Diseases  Pathological Processes  Body site for diseases  Diseases by staging  Risk factors Anatomy  Is-a, part-of  Granular relationship Biological Processes  Ontology  Classification Swiss-Prot proteins  Annotation: function, structure, mutation SNOMED GO FMA

ifomis.org Levels of granularity in biomedical ontology Populationenvironmentscreening PersonRace, age, disease, symptom ADL, working, treatment, prevention OrganLiver, lung, organ part, signHeart beat, digestion, surgery TissueElasticity,Turgor, StrengthResorption, protection CellBone cell, Alveolar cell Cell size, bacterium Fagocytosis, Cell growth, Reparation, hormone production SubcellularCell membrane, Protein DNA, Oncogene, Protooncogene, Virus, oncogenic molecule Transcription Splicing Mutation Gene regulation Granularity levelContinuantsOccurrents

ifomis.org SWISS-PROT and OMIM databases have little capability to support reasoning which crosses levels of granularity also, like SNOMED and GO, they offer no facility for reasoning about time and instances

ifomis.org TNM Staging Information – T1: The tumor invades the submucosa, the second layer of the large intestine. – T2: The tumor invades the muscularis propria. …

ifomis.org We need an ontological framework with the facility to deal with instance-based information drawn from Patient Records TNM Staging Information Risk factors (Age, Family history) Localization of Tumor (Organ affected, Tissues involved) Pathology (Gross and Miscroscopic pathology, Vessels involved, Nerves involved, Cell types, Nuclear characteristics)

ifomis.org Basic Formal Ontology glues the whole thing together at different levels of granularity, from molecular to whole organism level at different stages in time