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VT

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Medical Ontology

Barry Smith

http://ifomis.de

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IFOMIS

Institute for Formal Ontology and Medical Information Science

Faculty of Medicine

University of Leipzig

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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

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Reference Ontology

a theory of the tertium quid

– called reality –

needed to hand-callibrate database/terminology systems

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Methodology

Get ontology right first

(realism; descriptive adequacy; rather powerful logic);

solve tractability problems later

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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)

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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

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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

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Aristotle

Der erste Ontologe

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Eine biologische Ontologie

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Linné

1763: Genera Morborum

(Nosologie

oder

Ontologie der Krankheitsarten)

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Q: Warum “Ontologie” in der medizinischen Informatik?

A: Das Turm von Babel-Problem der Informationssysteme

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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?

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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)

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Dem Computer fehlt praktisches Wissen

Wie können in Medizininformations-systemen isolierte Datenartefakte zu konsistentem und anwendbarem Wissen integriert werden?

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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 ...

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Gegenwärtige Lösungen

Standardisierte Terminologien

UMLS

SNOMED

ICD-10

Gene Ontology

Digital Anatomist

usw.

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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

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Database and terminology standardization

is desparately needed in medical and bioinformatics

to enable the huge amounts of existing data to be fused together automatically

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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?

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Zentrale Schaltstelle

UMLS

Universal Medical Language System

National Library of Medicine

Bethesda, MD

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UMLS Metathesaurus

eine riesige Kombination verschiedener maschinenlesbarer Quellterminologien

800,000 Begriffe

10 Mio. Beziehungen

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Beispiele für Quell-Terminologien

SNOMED-RT

Systematized Nomenclature of Medicine

MeSH

Medical Subject Headings

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is_a trees

hormone

peptide hormone digestive hormone

adrenocorticotropin glycopeptide hormone

follicle-stimulating hormone

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is_a = ist ein / ist von der Art

Diabetes Melletus is_a Disease

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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)

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Terminological Incompatibilities

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Representation of Blood in SNOMED

Blood is_a Tissue

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Representation of Blood in MeSH

Blood is_a Bodily Fluid

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Bad CodingIncompatibilities

Context-Dependence

Standardized Terminologies must be used properly

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people are lazy and idiosyncratic

Sie machen SchreibfehlerJeder pflegt seine eigene Terminologie, die sich mehr oder weniger von der anderer Akteure unterscheidet Sie verwenden verschiedene natürlich-sprachliche Darstellungen der gleichen medizinischen Phänomena

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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

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The IFOMIS Contribution

help to improve standardizations through constructive criticism based on robust ontological principles

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UMLS Metathesaurus

eine riesige Kombination verschiedener maschinenlesbarer Quellterminologien

UMLS Semantic NetworkSemantic Network

bestehend aus 134 Semantic TypesSemantic Types

soll Ordnung in diesem Wust schaffen

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UMLS Semantic Network

entity event

physical conceptual entity entity

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conceptual entity

Organism Attribute

Finding

Idea or Concept

Occupation or Discipline

Organization

Group

Group Attribute

Intellectual Product

Language

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conceptual entity

Organism Attribute

Finding

Idea or Concept

Occupation or Discipline

Organization

Group

Group Attribute

Intellectual Product

Language

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Idea or ConceptFunctional ConceptQualitative ConceptQuantitative ConceptSpatial Concept

Body Location or RegionBody Space or JunctionGeographic AreaMolecular Sequence

Amino Acid SequenceCarbohydrate SequenceNucleotide Sequence

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INNSBRUCK

is an Idea or Concept

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Idea or ConceptFunctional ConceptQualitative ConceptQuantitative ConceptSpatial Concept

Body Location or RegionBody Space or JunctionGeographic AreaMolecular Sequence

Amino Acid SequenceCarbohydrate SequenceNucleotide Sequence

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Confusion of Ontology and Epistemology

Physical Entity

Chemical Entity

Chemical Chemical

Viewed Viewed

Structurally Functionally

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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

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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

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The goal

Formulate clear principles for building ontologies

Reconstitute the UMLS Semantic Types on the basis of these principles

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Zusammenarbeit mit der National Library of Medicine

Revision der UMLS Semantic Types und der Gene Ontology

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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

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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

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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

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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?)

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Definition of Biological Process

“A phenomenon marked by changes that lead to a particular result, mediated by one or more gene products”

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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?

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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)

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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”

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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”.

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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

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SNAP and SPAN

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SNAP and SPAN

Substances and processesContinuants and occurrents

In preparing an inventory of realitywe keep track of these two different categories of entities in two different ways

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Substances and processes exist in time in different ways

substance

t i m

e

process

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Need for different perspectives

Not one ontology, but a multiplicity of complementary ontologies

Cf. Quantum mechanics: particle vs. wave ontologies

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SNAPshot Video (SPAN)ontology ontology

substance

t i m

e

process

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SNAP and SPAN

stocks and flows

commodities and services

product and process

anatomy and physiology

synchrony and diachrony

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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

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SNAP: Entities existing in toto at a time

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Three kinds of SNAP entities

• Substances

• Dependent SNAP entities (qualities, functions, roles, powers …)

• Spatial regions, Contexts, Niches

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FunctionsThe function of the

heart is to pump blood

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SNAP

Fiat part of substanceExtremity (hand, arm)

Bodily System

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SPAN: Entities extended in time

SPANEntity extended in time

Portion of Spacetime

Fiat part of process *First phase of a clinical trial

Spacetime worm of 3 + Tdimensions

occupied by life of organism

Temporal interval *projection of organism’s life

onto temporal dimension

Aggregate of processes *Clinical trial

Process[±Relational]

Circulation of blood,secretion of hormones,course of disease, life

Processual Entity[Exists in space and time, unfolds

in time phase by phase]

Temporal boundary ofprocess *

onset of disease, death

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SPAN: Entities extended in time

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SPAN: Entities extended in time

FunctioningThe heart’s pumping

of blood

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Granularity

spatial region substance

parts of substances are always substances

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Granularity

spatial region substance

parts of spatial regions are always spatial regions

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Granularity

process

parts of processes are always processes

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MORAL

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

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

John’s lifesubstance John

physiological processes

sustaining in existence

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DIGESTIVE SYSTEM

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RESPIRATORY SYSTEM

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URINARYSYSTEM

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IMMUNE SYSTEM

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CIRCULATORY SYSTEM

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CIRCULATORY SYSTEM (Principal Organs)

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

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ENDOCRINESYSTEM

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Bodily Systems are Component Parts of Bodies

respiratorydigestive skeletal circulatorymusculatory immune

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A system for keeping your jewels safe

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Bodily Systems interconnect

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Systems are SNAP entitiesThey are dependent continuantsWe can take photographs of them

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The Monarchic System of Government