About ontologies

Melissa Haendel

And who am I that I am giving you this talk?

Melissa Haendel

Anatomist, developmental neuroscientist, molecular biologist, curator, ontologist

Most ontologists become ontologists because they have a need to classify and compute on a specific domain

Information retrieval from text-based resources is hard:

OMIM Query # of records“large bone” 785"enlarged bone" 156"big bones" 16"huge bones" 4"massive bones" 28"hyperplastic bones" 12"hyperplastic bone" 40"bone hyperplasia" 134"increased bone growth" 612

MouseEcotope GlyProt

DiabetInGene

GluChem

sphingolipid transporter

activity

Use of the same defined term indicates the same meaning under different annotation circumstances

Common vocabularies allow grouping of disparate data

http://www.mkbergman.com/?m=20070516

The controlled vocabulary spectrum

Bottom line: you get what you pay for. Ontologies are expensive but powerful.

OBO

Why build an ontology? A simple example

Number of genes annotated to each of the following brain parts in an ontology:

brain 20part_of hindbrain 15part_of rhombomere 10

Query brain without ontology 20Query brain with ontology 45

Ontologies can facilitate grouping and retrieval of data

An ontology is a classification vocabularyPhilosophers: Ontology = The study of being as a branch of philosophy

Bioinformaticists: Domain ontology = representing a specific knowledge base

Features of ontologies:

1. Terms are defined2. Terms are arranged in a

hierarchy3. Relationships between the

terms are defined4. Expressed in a knowledge

representation language

Some well known ontologies are:SnoMED, Foundational Model of Anatomy, Gene Ontology, Linnean Taxonomy of species

Defining ontology classes, a beginner’s guide

An X =Y that has one or more differentiating characteristics.where Y is the is_a parent of X.

Definition: Blue cylinder = Cylinder that is blue.

Definition: cylinder = Surface formed by the set of lines perpendicular to a plane, which pass through a given circle in that plane.

is_a

These types are Disjoint: A cylinder can be either blue or red by definition, but not both.Definitions specify necessary and sufficient conditions.

is_a

Definition: Red cylinder = Cylinder that is red.

Y

X

Subsumption reasoning:The simplest ontology reasoning

is_a

entityentity

organismorganism

catcat

mammalmammal

animalanimalis_a

is_a

is_ahumanhuman

is_a

instance_of instance_of

Peanut Chris Shaffer

Hierarchy typesSimple taxonomy

Directed acyclic graph

Subject —— Property —— Object

brain (class) has_part neuron (class)PloS 2009 (instance) has_author Melissa (instance)Chris (instance) owns red tie (instance)

Ontology classes, instances, and relations are stored as sentences

The True Path Rule

cuticle synthesis--[i] chitin metabolismcell wall biosynthesis--[i] chitin metabolism----[i] chitin biosynthesis----[i] chitin catabolism

chitin metabolism--[i] chitin biosynthesis--[i] chitin catabolism--[i] cuticle chitin metabolism----[i] cuticle chitin biosynthesis----[i] cuticle chitin catabolism--[i] cell wall chitin metabolism----[i] cell wall chitin biosynthesis----[i] cell wall chitin catabolism

GO Before: GO After:

BUT: A fly chitin synthase could be annotated to chitin biosynthesis, and appear in a query for genes annotated to cell wall biosynthesis (and its children), which makes no sense because flies don't have cell walls.

BUT: A fly chitin synthase could be annotated to chitin biosynthesis, and appear in a query for genes annotated to cell wall biosynthesis (and its children), which makes no sense because flies don't have cell walls.

NOW: all the child terms can be followed up to chitin metabolism, but cuticle chitin metabolism terms do not trace back to cell wall terms, so all the paths are true.

NOW: all the child terms can be followed up to chitin metabolism, but cuticle chitin metabolism terms do not trace back to cell wall terms, so all the paths are true.

The pathway from a child term all the way up to its top level parent(s) must be universally true.

Where does the True Path Rule come from?Transitivity. Some relations are transitive, and apply across all levels of the hierarchy.

For example, a cat is_a mammal, and a mammal is_a vertebrateSOa cat is_a vertebrate

=> This is the true path rule and is because the is_a relation is transitive.

Some properties are not transitive.

For example, head has_quality round.and,

head part_of organism. So is the organism round? Of course not!

BUT, eyes are part_of head, and head part_of organism, SO eye part_of organism is true, because part_of is a tranistive relation.

Relations are logically defined in a common relation ontology or within each ontology that uses them.

≠>

Domain ontologies are organized according to upper ontologies that specify the general types of things that exist

RELATION TO TIME

GRANULARITY

CONTINUANT OCCURRENT

INDEPENDENT DEPENDENT

ORGAN ANDORGANISM

Organism(NCBI

Taxonomy)

Anatomical Entity

(FMA, CARO)

OrganFunction

(FMP, CPRO) Phenotypic Quality(PaTO)

Biological Process(GO)

CELL AND CELLULAR COMPONENT

Cell(CL)

Cellular Component(FMA, GO)

Cellular Function(GO)

MOLECULEMolecule

(ChEBI, SO,RnaO, PrO)

Molecular Function(GO)

Molecular Process(GO)

=> Classification according to these higher level types helps ensure the True Path Rule holds

UniversalityOften, the order of the terms in an assertion will matter:

We can assert

adult transformation_of child

but not

child transformation_of adult

More about using ontology classes and relationsUnivocityTerms should have the same meanings on every occasion of use. (= They should refer to the same universal types)

Basic ontological relations such as is_a and part_of should be used in the same way by all ontologies

Common ontology languages

OWL is a recognized standard, more toolsavailable, less restricted expressivity

OBO simple, more easily readable, used by many biologists, restricted expressivity

</owl:Class> <owl:Class rdf:about="http://purl.obolibrary.org/obo/OBI_0000626"><!-- DNA sequencing --> <owl:disjointWith> <owl:Class rdf:about="http://purl.obolibrary.org/obo/OBI_0000705"/><!-- Edman degradation --> </owl:disjointWith> <rdfs:label rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >DNA sequencing</rdfs:label> <obo:IAO_0000111 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >DNA sequencing</obo:IAO_0000111> <obo:IAO_0000119 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >OBI Branch derived</obo:IAO_0000119> <obo:IAO_0000115 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >DNA sequencing is a sequencing process which uses deoxyribonucleic acid as input and results in a the creation of DNA sequence information artifact using a DNA sequencer instrument.</obo:IAO_0000115> <obo:IAO_0000114 rdf:resource="http://purl.obolibrary.org/obo/IAO_0000123"/> <rdfs:subClassOf> <owl:Restriction> <owl:onProperty> <owl:ObjectProperty rdf:about="http://purl.obolibrary.org/obo/OBI_0000293"/><!-- has_specified_input --> </owl:onProperty> <owl:someValuesFrom> <owl:Class> <owl:intersectionOf rdf:parseType="Collection"> <owl:Class rdf:about="http://purl.org/obo/owl/CHEBI#CHEBI_16991"/> <owl:Restriction> <owl:someValuesFrom> <owl:Class rdf:about="http://purl.obolibrary.org/obo/OBI_0000067"/><!-- evaluant role --> </owl:someValuesFrom> <owl:onProperty> <owl:ObjectProperty rdf:about="http://purl.obolibrary.org/obo/OBI_0000316"/><!-- has_role --> </owl:onProperty> </owl:Restriction> </owl:intersectionOf> </owl:Class> </owl:someValuesFrom> </owl:Restriction> </rdfs:subClassOf> <rdfs:subClassOf> <owl:Class rdf:about="http://purl.obolibrary.org/obo/OBI_0600047"/><!-- sequencing assay --> </rdfs:subClassOf> <rdfs:subClassOf> <owl:Restriction> <owl:someValuesFrom> <owl:Class> <owl:intersectionOf rdf:parseType="Collection"> <owl:Class rdf:about="http://purl.obolibrary.org/obo/IAO_0000030"/> <owl:Restriction> <owl:someValuesFrom rdf:resource="http://purl.obolibrary.org/obo/OBI_0000811"/><!-- primary structure of DNA macromolecule --> <owl:onProperty rdf:resource="http://purl.obolibrary.org/obo/IAO_0000136"/> </owl:Restriction> </owl:intersectionOf> </owl:Class> </owl:someValuesFrom> <owl:onProperty> <owl:ObjectProperty rdf:about="http://purl.obolibrary.org/obo/OBI_0000299"/><!-- has_specified_output --> </owl:onProperty> </owl:Restriction> </rdfs:subClassOf> <obo:IAO_0000117 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >Philippe Rocca-Serra</obo:IAO_0000117> <rdfs:subClassOf> <owl:Restriction> <owl:onProperty> <owl:ObjectProperty rdf:about="http://purl.obolibrary.org/obo/OBI_0000417"/><!-- achieves_planned_objective --> </owl:onProperty> <owl:someValuesFrom rdf:resource="http://purl.obolibrary.org/obo/OBI_0000441"/><!-- assay objective --> </owl:Restriction> </rdfs:subClassOf> <obo:IAO_0000112 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >Genomic deletions of OFD1 account for 23% of oral-facial-digital type 1 syndrome after negative DNA sequencing. Thauvin-Robinet C, Franco B, Saugier-Veber P, Aral B, Gigot N, Donzel A, Van Maldergem L, Bieth E, Layet V, Mathieu M, Teebi A, Lespinasse J, Callier P, Mugneret F, Masurel-Paulet A, Gautier E, Huet F, Teyssier JR, Tosi M, Frébourg T, Faivre L. Hum Mutat. 2008 Nov 19. PMID: 19023858</obo:IAO_0000112> </owl:Class> <owl:Class rdf:about="http://purl.obolibrary.org/obo/OBI_0000743"><!-- immune response assay --> <owl:equivalentClass> <owl:Class> <owl:intersectionOf rdf:parseType="Collection"> <owl:Restriction> <owl:someValuesFrom> <owl:Class> <owl:intersectionOf rdf:parseType="Collection"> <owl:Class rdf:about="http://purl.obolibrary.org/obo/IAO_0000109"/> <owl:Restriction> <owl:onProperty rdf:resource="http://purl.obolibrary.org/obo/IAO_0000136"/> <owl:someValuesFrom rdf:resource="http://purl.org/obo/owl/GO#GO_0006955"/> </owl:Restriction> </owl:intersectionOf> </owl:Class> </owl:someValuesFrom> <owl:onProperty> <owl:ObjectProperty rdf:about="http://purl.obolibrary.org/obo/OBI_0000299"/><!-- has_specified_output --> </owl:onProperty> </owl:Restriction> <owl:Restriction> <owl:onProperty> <owl:ObjectProperty rdf:about="http://purl.obolibrary.org/obo/OBI_0000417"/><!-- achieves_planned_objective --> </owl:onProperty> <owl:someValuesFrom rdf:resource="http://purl.obolibrary.org/obo/OBI_0000441"/><!-- assay objective --> </owl:Restriction> </owl:intersectionOf> </owl:Class> </owl:equivalentClass> <obo:IAO_0000114 rdf:resource="http://purl.obolibrary.org/obo/IAO_0000124"/> <rdfs:label rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >immune response assay</rdfs:label> <obo:IAO_0000111 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >immune response assay</obo:IAO_0000111> <obo:IAO_0000115 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >Is an assay with the objective to determine information about an immune response</obo:IAO_0000115> <rdfs:subClassOf rdf:resource="http://purl.obolibrary.org/obo/OBI_0000070"/><!-- assay -->

</owl:Class> <owl:Class rdf:about="http://purl.obolibrary.org/obo/OBI_0000626"><!-- DNA sequencing --> <owl:disjointWith> <owl:Class rdf:about="http://purl.obolibrary.org/obo/OBI_0000705"/><!-- Edman degradation --> </owl:disjointWith> <rdfs:label rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >DNA sequencing</rdfs:label> <obo:IAO_0000111 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >DNA sequencing</obo:IAO_0000111> <obo:IAO_0000119 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >OBI Branch derived</obo:IAO_0000119> <obo:IAO_0000115 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >DNA sequencing is a sequencing process which uses deoxyribonucleic acid as input and results in a the creation of DNA sequence information artifact using a DNA sequencer instrument.</obo:IAO_0000115> <obo:IAO_0000114 rdf:resource="http://purl.obolibrary.org/obo/IAO_0000123"/> <rdfs:subClassOf> <owl:Restriction> <owl:onProperty> <owl:ObjectProperty rdf:about="http://purl.obolibrary.org/obo/OBI_0000293"/><!-- has_specified_input --> </owl:onProperty> <owl:someValuesFrom> <owl:Class> <owl:intersectionOf rdf:parseType="Collection"> <owl:Class rdf:about="http://purl.org/obo/owl/CHEBI#CHEBI_16991"/> <owl:Restriction> <owl:someValuesFrom> <owl:Class rdf:about="http://purl.obolibrary.org/obo/OBI_0000067"/><!-- evaluant role --> </owl:someValuesFrom> <owl:onProperty> <owl:ObjectProperty rdf:about="http://purl.obolibrary.org/obo/OBI_0000316"/><!-- has_role --> </owl:onProperty> </owl:Restriction> </owl:intersectionOf> </owl:Class> </owl:someValuesFrom> </owl:Restriction> </rdfs:subClassOf> <rdfs:subClassOf> <owl:Class rdf:about="http://purl.obolibrary.org/obo/OBI_0600047"/><!-- sequencing assay --> </rdfs:subClassOf> <rdfs:subClassOf> <owl:Restriction> <owl:someValuesFrom> <owl:Class> <owl:intersectionOf rdf:parseType="Collection"> <owl:Class rdf:about="http://purl.obolibrary.org/obo/IAO_0000030"/> <owl:Restriction> <owl:someValuesFrom rdf:resource="http://purl.obolibrary.org/obo/OBI_0000811"/><!-- primary structure of DNA macromolecule --> <owl:onProperty rdf:resource="http://purl.obolibrary.org/obo/IAO_0000136"/> </owl:Restriction> </owl:intersectionOf> </owl:Class> </owl:someValuesFrom> <owl:onProperty> <owl:ObjectProperty rdf:about="http://purl.obolibrary.org/obo/OBI_0000299"/><!-- has_specified_output --> </owl:onProperty> </owl:Restriction> </rdfs:subClassOf> <obo:IAO_0000117 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >Philippe Rocca-Serra</obo:IAO_0000117> <rdfs:subClassOf> <owl:Restriction> <owl:onProperty> <owl:ObjectProperty rdf:about="http://purl.obolibrary.org/obo/OBI_0000417"/><!-- achieves_planned_objective --> </owl:onProperty> <owl:someValuesFrom rdf:resource="http://purl.obolibrary.org/obo/OBI_0000441"/><!-- assay objective --> </owl:Restriction> </rdfs:subClassOf> <obo:IAO_0000112 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >Genomic deletions of OFD1 account for 23% of oral-facial-digital type 1 syndrome after negative DNA sequencing. Thauvin-Robinet C, Franco B, Saugier-Veber P, Aral B, Gigot N, Donzel A, Van Maldergem L, Bieth E, Layet V, Mathieu M, Teebi A, Lespinasse J, Callier P, Mugneret F, Masurel-Paulet A, Gautier E, Huet F, Teyssier JR, Tosi M, Frébourg T, Faivre L. Hum Mutat. 2008 Nov 19. PMID: 19023858</obo:IAO_0000112> </owl:Class> <owl:Class rdf:about="http://purl.obolibrary.org/obo/OBI_0000743"><!-- immune response assay --> <owl:equivalentClass> <owl:Class> <owl:intersectionOf rdf:parseType="Collection"> <owl:Restriction> <owl:someValuesFrom> <owl:Class> <owl:intersectionOf rdf:parseType="Collection"> <owl:Class rdf:about="http://purl.obolibrary.org/obo/IAO_0000109"/> <owl:Restriction> <owl:onProperty rdf:resource="http://purl.obolibrary.org/obo/IAO_0000136"/> <owl:someValuesFrom rdf:resource="http://purl.org/obo/owl/GO#GO_0006955"/> </owl:Restriction> </owl:intersectionOf> </owl:Class> </owl:someValuesFrom> <owl:onProperty> <owl:ObjectProperty rdf:about="http://purl.obolibrary.org/obo/OBI_0000299"/><!-- has_specified_output --> </owl:onProperty> </owl:Restriction> <owl:Restriction> <owl:onProperty> <owl:ObjectProperty rdf:about="http://purl.obolibrary.org/obo/OBI_0000417"/><!-- achieves_planned_objective --> </owl:onProperty> <owl:someValuesFrom rdf:resource="http://purl.obolibrary.org/obo/OBI_0000441"/><!-- assay objective --> </owl:Restriction> </owl:intersectionOf> </owl:Class> </owl:equivalentClass> <obo:IAO_0000114 rdf:resource="http://purl.obolibrary.org/obo/IAO_0000124"/> <rdfs:label rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >immune response assay</rdfs:label> <obo:IAO_0000111 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >immune response assay</obo:IAO_0000111> <obo:IAO_0000115 rdf:datatype="http://www.w3.org/2001/XMLSchema#string" >Is an assay with the objective to determine information about an immune response</obo:IAO_0000115> <rdfs:subClassOf rdf:resource="http://purl.obolibrary.org/obo/OBI_0000070"/><!-- assay -->

[Term]id: OBI:0000626name: DNA sequencingdef:"DNA sequencing is a sequencing process which uses deoxyribonucleic acid as input and results in a the creation of DNA sequence information artifact using a DNA sequencer instrument." [OBI:sourced "OBI Branch derived"]is_a: OBI:0600047 ! sequencing assay

[Term]id: OBI:0000626name: DNA sequencingdef:"DNA sequencing is a sequencing process which uses deoxyribonucleic acid as input and results in a the creation of DNA sequence information artifact using a DNA sequencer instrument." [OBI:sourced "OBI Branch derived"]is_a: OBI:0600047 ! sequencing assay

Ontology Lookup Service at EBI

http://www.ebi.ac.uk/ontology-lookup/

Bioportal at the NCBO

http://bioportal.bioontology.org/

Ontology Editors (and viewers)

http://oboedit.org/

OBOEdit- OBO ontology editor and viewer

Protégé - OWL ontology editor and viewer

http://protege.stanford.edu/

Ontologies can help reconcile annotation inconsistencies

Developmental Biology, Scott Gilbert, 6th ed.

Using ontologies for error checking

Text match mappingFruit fly ‘tibia’ Human ‘tibia’

UBERON: tibia

UBERON: bone

is_a

is_a

is_a

Vertebrata

Drosophila melanogaster

part_of

Homo sapiens

is_a

only_in_taxon

part_of

NOT is_a

Using ontologies for alignment of similar vocabularies

Information Content (IC) is based on depth within the ontology and annotation frequency

Using ontologies for computation

Why do we need all these rules and standards for ontology use and construction?

• Automatic reasoning to infer related classes• Annotation consistency• Error checking• Alignment with other ontologies • Computation

Ontologies must be intelligible to both:

Humans Machines