Clinical Bioinformatics for combatting cancer: the place of ontology.

dasypygalstockingsBiotechnology

Oct 2, 2013 (3 years and 10 months ago)

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Ontologie
-
basierte
Qualitätssicherung
medizinischer Terminologien

Barry Smith


with thanks to Werner Ceusters,
Anand Kumar and Cornelius
Rosse

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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

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UMLS Metathesaurus traps

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Problem: Confusion of concepts
and entities in reality

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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).


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UMLS
-
Semantic Types:

blood pressure is an
Organism
Function
,

cardiac output is a
Laboratory or
Test Result
or
Diagnostic
Procedure


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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


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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
.

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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

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Confused treatment of objects
and processes

diagnostische_endoskopische_Untersuchung
_eines_Mediastinums_NOS





is_a Mediastinoskop
.

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Confusion of object with
knowledge about object

Kontrazeption is_a funktionaler_Befund

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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




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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

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Confusion of part_of and
overlaps_with

Struktur_des_Nervus_tibialis



is_a

Oberschenkelteil


Struktur_des_Nervus_tibialis



is_a

Unterschenkelstruktur


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Missed subsumption detection

Missing: is_a neoplasm of heart

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Are these just isolated
examples of errors?

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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
:

B
iomedical objects to facilitate the communication
and integration of information from the various
initiatives supported by the NCICB

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caBIO architecture

Connectivity at programming interface level

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Instead of building an ontology
of cancer


the NCI builds an ontology (or a
‘model’) of the data in the NCI’s
own computers

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NCI
Thesaurus


a biomedical thesaurus created
specifically to meet the needs of the
NCI


semantically modeled cancer
-
related
terminology built using

Description
Logic

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Search for “cancer”

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Missed subsumption detection

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Recall SNOMED confusion of
‘part’ and ‘structure’

Struktur_des_Nervus_tibialis



is_a

Oberschenkelteil


Struktur_des_Nervus_tibialis



is_a

Unterschenkelstruktur


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Confusion of ‘part’ and
‘structure’ and ‘system’ and
‘substance’

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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 ?

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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, ...

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Action is_a Conceptual Entity


And is_a Conceptual Entity



Swimming is healthy and contains 8 letters

Conceptual entity

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Definition of “cancer
gene”

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NCI Thesaurus architecture

Disease

Breast

Breast 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 ?

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Confusion of objects and the
states in which they participate

Disease

Breast

Breast neoplasm

Disease
-
has
-
associated
-
anatomy

ISA

Findings
-
And
-

Disorders
-
Kind

Anatomy
-
Kind

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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.


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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

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“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.

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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

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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

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Levels of granularity in

biomedical ontology

Population

environment

screening

Person

Race, age, disease,
symptom

ADL, working,
treatment, prevention

Organ

Liver, lung, organ part, sign

Heart beat, digestion,
surgery

Tissue

Elasticity,Turgor, Strength

Resorption, protection

Cell

Bone cell, Alveolar cell

Cell size, bacterium

Fagocytosis, Cell
growth, Reparation,
hormone production

Subcellular

Cell membrane, Protein

DNA, Oncogene,
Protooncogene,

Virus, oncogenic molecule

Transcription

Splicing

Mutation

Gene regulation

Granularity level

Continuants

Occurrents

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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

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TNM Staging Information



T
1
:

The

tumor

invades

the

submucosa,

the

second

layer

of

the

large

intestine
.



T2: The tumor invades the muscularis propria.




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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)

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Basic Formal Ontology glues the
whole thing together

at different
levels of granularity
, from
molecular to whole organism level

at different
stages
in time