Biomedical Ontologies

Hanene Boussi Rahmouni,

Biomedical Engineering, Medical Informatics
Higher Institute of Medical Technologies of Tunis
 Overview
❖ Knowledge Representation in Biology
❖ What is ontology?
❖ What is biomedical ontology?
❖ Examples of Biomedical and Medical Ontologies
❖How an ontology is it generated?
❖How is it used for annotation?
❖Why is it necessary?
❖How to use it?

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 Ontology:
onto-, of being or existence; -logy, study.
Greek origin; Latin, ontologia,1606

• In philosophy, it seeks to describe basic categories

and relationships of being or existence to define
entities and types of entities within its framework:
– What do you know? How do you know it?
– What is existence? What is a physical object?
– What constitutes the identity of an object? ……
• Central goal is to have a definitive and exhaustive
classification of all entities.

“The science of what is, of the kinds and structures of objects,

properties, events, processes and relations in every area of reality”
– Barry Smith, U Buffalo
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4
Tree of Porphyry with Aristotle’s
Categories

Aristotle, 384 BC – 322 BC

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 In computer and information science
• Ontology is a data model that represents a set of
concepts within a domain and the relationships
between those concepts. It is used to reason about
the objects within that domain.
Most ontologies describe individuals
(instances), classes (concepts), is_a
attributes, and relations

Classes

Relations

Attributes
Classes
e.g. color,
engine, door… (concepts)

Individuals (instances) your Ford, my Ford, his Ford…

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 What are ontology useful for?
Ontology is a form of knowledge representation about
the world or some part of it.
• Terminology management
• Integration, interoperability, and sharing of data
– promote precise communication between scientists
– enable information retrieval across multiple resources
• Knowledge reuse and decision support
– extend the power of computational approaches to perform
data exploration, inference, and mining

Biomedical Terminology vs. Biomedical Ontology

• UMLS (unified medical language system)
• MeSH (medical subject heading)
• NCI Thesaurus
• SNOMED / SNODENT
• Medical WordNet 7
 Controlled vocabularies

Glossary: A glossary, also known as a vocabulary, is an alphabetical list of terms in a particular domain of
knowledge with the definitions for those terms.
Taxonomy: is the science of classification.
Thesaurus: hierarchical taxonomy with definitions and preferred terms
Ontology: encodes the knowledge of the domain in such a way that the knowledge can be
understood by a computer. This is the basic idea of ontology.

To summarise:

An ontology is the meaning of words and relationships of concepts in a thesaurus, which resides
within a taxonomy, which resides within a controlled vocabulary, which resides within
the ontology of the world.

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 Ontology Enables
Large-Scale Biomedical Science
The center of two major activities currently in
biomedical research:
• Structured representation of biomedicine:
– For different types of entities and relations to describe
biomedicine (ontology content curation).
• Annotation: using ontologies to summarize and describe
biomedical experimental results to enable:
– Integration of their data with other researchers’
results
– Cross-species analyses

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Gene Ontology (GO)

what makes it
so wildly
successful ?

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 GO Consortium

[Link]

• The Gene Ontology was originally constructed in 1998 by

a consortium of researchers studying the genome of three
model organisms:
– Drosophila melanogaster (fruit fly) (FlyBase)
– Mus musculus (mouse) (MGD)
– Saccharomyces cerevisiae (yeast) (SGD)
• Many other model organism databases have joined the
GO consortium, contributing:
– development of the ontologies
– annotations for the genes of one or more organisms
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Need for annotation of genome sequences
• What is Gene Ontology? GO provides controlled vocabulary to
describe gene and gene product attributes in any organism – how gene
products behave in a cellular context
Three key concepts: [Currently total 25804 GO terms] (Oct. 2008)
• Biological process: series of events accomplished by one or more
ordered assemblies of molecular functions, e.g. signal transduction, or
pyrimidine metabolism, and alpha-glucoside transport. [total: 15161]
• Molecular function: describes activities, such as catalytic or binding
activities, that occur at the molecular level. Activities that can be
performed by individual gene products, or by assembled complexes of
gene products; e.g. catalytic activity, transporter activity. [total: 8425]
• Cellular component: a component of a cell that it is part of some larger
object, maybe an anatomical structure (e.g. ER or nucleus) or a gene
product group (e.g. ribosome, or a protein dimer). [total: 2218]

• GO annotation
- Characterization of gene products using GO terms
- Members submit their data which are available at GO
website. 14
 GO Representation:
Tree or Network?
root GO is a network structure

Node, a
A concept
or a term
C
C has two
parents, A
and B
B
Relations:
is_a, or C
part_of Leaf
node

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[Link] 16
 GO search and display tool

GO term (GO:0006366):
mRNA transcription from RNA polymerase II promoter

Leaf
node

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 Human p53 – GO annotation
(UniProtKB:P04637)

GO:0006289:nucleotide-excision repair [PMID:7663514; evidence:IMP]

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 A real example:
Build a simple tree
Let the classifier organise it
If you want more abstractions,
just add new definitions
(re-use existing data)

“Diseases linked to abnormal

proteins”
And let the classifier work again
And again – even for a quite
different category

“Diseases linked genes

described in the mouse”
Summary: Why Normalise?
Why use a Classifier?
• To compose concepts
– Allow conceptual lego
• To manage polyhierarchies
– Adding abstractions (“axes”) as needed
– Normalisation
• Untangling
– labelling of “kinds of is-a”
• To avoid combinatorial explosions
– Keep bicycles from exploding
• To manage context
– Cross species, Cross disciplines, Cross studies
• To check consistency and help users find errors
 Task: Make Pneumonitis and
Pneumonias in various
variations

• Question 1: What is “Pneumonia”

and what is “Pneumonitis”
– Look it up
• e.g. Google define: pneumonitis

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 Task: Make Pneumonitis and
Pneumonias in various variations

►Many definitions on the web, but this summarises them for

our purposes.
►Write your own paraphrases:

►“Pneumonitis” is an “Inflammation of the lungs”

►“Pneumonia” is an “inflammation of the lungs caused by
an infection”

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 First defintion of pneumonitis
• “Inflammation of the lung”
– Find Inflammation
• CTRL or CMND F in class hierarchy

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 Create “Pneumonitis”
• Create a new subclass of Inflammation
– In the comment box type something like
“Pneumonitis” = “Inflammation of lung”
• ALWAYS add a free text paraphrase of what
you are modelling
– Add the restriction
• has_locus SOME Lung

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 Create pneumonia
• “Pneumonia” is a pneumonitis is the outcome of an
infection
– In this ontology we use “is_outcome_of” for
“cause”

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 Bacterial pneumonia
• First attempt
– “Pneumonia caused by a bacteria”
• But need to rephrase to fit the ontology
– “Pneumonia that is the outcome of an infection by bacteria”
• In this ontology “by” translates to the property “has_actor”
– Processes have actors and objects

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 Class/Concept Constructors

C is a concept (class); P is a role (property); xi is an individual/nominal

XMLS datatypes as well as classes in 8P.C and 9P.C
Restricted form of DL concrete domains
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 Ontology Axioms

• OWL ontology equivalent to DL KB (Tbox + Abox)

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 By analogy make viral pnemonia and mixed
pneumonia
• Mixed pneumonia is a pneumonia that is caused by both virus and
pneumonia
– How to say this

– WARNING
• wrong: has_actor SOME (Virus AND Bacterium)
– Nothing is both a virus and a bacteria

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 Classify and check
• Be sure that all classes are defined
– defined

– primitive

• To convert from primitive to defined, cmnd-d or ctrtl-d (Mac

or PC)

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3
5
 Should get

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3
6
 “Pure bacterial pneumonia”
• Note that “Mixed pneumonia” is a kind of both bacterial and viral
pneumonia
– This is what our definition has said
• What if we want a pneumonia ONLY caused by bacteria.
– “A pneumonia that has_actor bacterium and only bacterium
• A variant of “vegetarian pizza”
– ... but the closure axiom is more complicated.

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 Classify and check

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3
8
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 What about “left lower lobe pneumonia”?
• First define lobar pneumonia as
– Pneumonia that has locus in a lobe of a lung
• “Lobe THAT is_subdivision_of SOME
Lung”
• But what then is a disorder of the lung
– Disorder THAT has_locus SOME Lung
• But what if I define an inflammation of a lobe of
the lung
– Inflammation THAT has_locus SOME
(Lobe THAT is_subdivision_of SOME
Lung)
– The classifier ought to organise it for us
40 • ... but it doesn’t.
 OWL means what it says
• Lobes are not lungs!
– Our definition of lung disorder is too narrow
• Almost always
Disorders of parts are disorders of the whole
• A broader definition of “Disorder_of_lung”
– Disorder THAT has_locus SOME
(Lung OR is_clinical_part_of SOME Lung)

►Almost OK, but still Inflammation of lobe of lung is not a

pneumonitis
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 Make the pattern consistent
• Redefine Pneumonitis
“An inflammation of the lung or any clinical part of the lung of the lung”

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4
2
 Almost correct, but...

• What about “Bronchitis” ?

– An inflammation of the bronchi (or any of their parts)
• Try it and see.

►Definition of “Pneumonitis” is now too broad

►Not just any part of the lung, but the “subdivisions” of the lung
► lobes, quadrants, bases, apices, etc.

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 The property hierarchy allows
multiple views

• The bronchus is a “component” of

the lung
• The lobe is a subdivision of the lung
• Redefine pneumonitis as an
inflammation of the lung or a
44 subdivision of the lung 4
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 Now reclassify

• Bronchitis is now a disorder of the

lung ( “lung disease”) but not a
pneumonitis
– As required.

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 Clinical partonomy and
pleuritis
• To an anatomist,
– the pleura are different organs from the lungs
• To a clinician,
– “Pleuritis”should be classified as a “Lung disease” or
“Disorder of the lung”
• “Pleuritis” - Inflammation of the pleura
• The Pleura
– function as part of the lung
– even though they are not physically part of the lung
• The property hierarchy copes with both views.

►Anything that is structurally a part of something is a clinical

part of it
►Anything that is functionally a part of something is a clinical
part of it
►etc.
46 ►BUT NOT VICE VERSA.
 Also affects modularity
• We have chosen to model functional parts with
physiology rather than with anatomy
– To stick with the FMA view as far as possible in the Anatomy module.
• So we add the fact that the pleur are functionals part of
the Lung in the physiologic_processes module rather
than the anatomy module
– Might even have a separate functional module
• We can add information to a class in a new module

Additions in
physiologica
l_
processes.o
wl

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 Create pleuritis and
classify
• Classify and
check results
– A disorder of
the lung but
not a bronchitis
or
pneumonitis.
• as required
– Anatomists &
Clinicians can
each have
their own view
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 An OWL2 Fragment
<owl:Class> <owl:intersectionOf rdf:parseType="Collection">
<owl:Class> <owl:oneOf rdf:parseType="Collection">
<owl:Thing rdf:about="#Tosca" /> <owl:Thing
rdf:about="#Salome" /> </owl:oneOf> </owl:Class>
<owl:Class> <owl:oneOf rdf:parseType="Collection">
<owl:Thing rdf:about="#Turandot" /> <owl:Thing
rdf:about="#Tosca" /> </owl:oneOf> </owl:Class>
</owl:intersectionOf> </owl:Class>

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 Normality and Negation
• What does it mean to be normal or abnormal?
– To have a disease
• We implement two notions -
– NonNormal - anything noteworthy
• Pathological - requiring medical intervention
– (including “watchful waiting” or an active decision not to
intervene)
» GALEN used “Intrinsically pathological”
but not needed in OWL
• Basic rules
– Pathological ➔ nonNormal
– Normal = NOT nonNormal
– nonPathological = NOT pathological

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5
0
 Normality and negation
• Basic rules
– Pathological ➔ nonNormal
– Normal = NOT nonNormal
– nonPathological = NOT pathological
• Remember
– subclassOf means “necessarily implies”
• so Pathological is a subclass of nonNormal
– See the definitions of Normal-nonNormal_quality in [Link]
• Let the classifier do the work...

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 Defining “disease” or “disorder”

• Hard, probably futile

– The words are used in many different ways
– Things referred to cross ontological boundaries
• Lesions - e.g tumours
• Processes - e.g. infection or inflammation
• Qualities - e.g. obstruction, malformation, elevation, ...
• Best just to say what is pathological
– let the classifier gather them up

• Also classify along multiple dimensions

– include as many abstractions as are useful, no more
and no less
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2
 Example from tiny tutorial
ontology

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 Summary
• Knowledge is fractal
– Enumeration is never ending
• The power of logic / OWL is composition and classification
• Normalise ontologies for re-use and maintenance
– Build DAGs (nets) out of Trees using classification
• Diseases of the parts are diseases of the whole
– ... but must be careful
• The property hierarchy can be used to support multiple views
• Some notions defy definition - e.g. “Disease”
– When in doubt describe, classify and look at the result

• Much more in the comments in the tutorial ontology

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