the relation ontology
DESCRIPTION
The Relation Ontology. Barry Smith. Concepts, Types and Frames. Concepts, Types and Frames. TLR2:MyD88 complex. has_output. TLR2-MyD88 binding. has_disposition. has_participant. TLR2. LTA binding. has_participant. MyD88. regulated_by. preceded_by. has_lower_level_granularity. - PowerPoint PPT PresentationTRANSCRIPT
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The Relation Ontology
Barry Smith
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Concepts, Types and Frames
Concepts Frames
TypesRelational Structures
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Concepts, Types and Frames
Concepts FramesLinguistic Approach
TypesRelational Structures
Scientific Approach
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has_lower_level_granularity
TLR2-MyD88binding TLR2has_participant
LTA bindinghas_disposition
TIR domain
has_part
TLR2-TLR2ligand
binding
TIR-TIRbinding
process
preceded_by
regulated_by
has_outp
ut
has_participant
TLR2:MyD88complex
MyD88
has_participant
TLR-2 signalling pathway
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5how to define relations such as this?
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Uses of ‘ontology’ in PubMed abstracts
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By far the most successful: The Gene Ontology
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MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDV
How to do biology across the genome?
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MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPIPSKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDSFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVVAGEAASSNHHQKISRVTRKRPREPKSTNDILVAGQKLFGSSFEFRDLHQLRLCYEIYMADTPSVAVQAPPGYGKTELFHLPLIALASKGDVEYVSFLFVPYTVLLANCMIRLGRRGCLNVAPVRNFIEEGYDGVTDLYVGIYDDLASTNFTDRIAAWENIVECTFRTNNVKLGYLIVDEFHNFETEVYRQSQFGGITNLDFDAFEKAIFLSGTAPEAVADAALQRIGLTGLAKKSMDINELKRSEDLSRGLSSYPTRMFNLIKEKSEVPLGHVHKIRKKVESQPEEALKLLLALFESEPESKAIVVASTTNEVEELACSWRKYFRVVWIHGKLGAAEKVSRTKEFVTDGSMQVLIGTKLVTEGIDIKQLMMVIMLDNRLNIIELIQGVGRLRDGGLCYLLSRKNSWAARNRKGELPPKEGCITEQVREFYGLESKKGKKGQHVGCCGSRTDLSADTVELIERMDRLAEKQATASMSIVALPSSFQESNSSDRYRKYCSSDEDSNTCIHGSANASTNASTNAITTASTNVRTNATTNASTNATTNASTNASTNATTNASTNATTNSSTNATTTASTNVRTSATTTASINVRTSATTTESTNSSTNATTTESTNSSTNATTTESTNSNTSATTTASINVRTSATTTESTNSSTSATTTASINVRTSATTTKSINSSTNATTTESTNSNTNATTTESTNSSTNATTTESTNSSTNATTTESTNSNTSAATTESTNSNTSATTTESTNASAKEDANKDGNAEDNRFHPVTDINKESYKRKGSQMVLLERKKLKAQFPNTSENMNVLQFLGFRSDEIKHLFLYGIDIYFCPEGVFTQYGLCKGCQKMFELCVCWAGQKVSYRRIAWEALAVERMLRNDEEYKEYLEDIEPYHGDPVGYLKYFSVKRREIYSQIQRNYAWYLAITRRRETISVLDSTRGKQGSQVFRMSGRQIKELYFKVWSNLRESKTEVLQYFLNWDEKKCQEEWEAKDDTVVVEALEKGGVFQRLRSMTSAGLQGPQYVKLQFSRHHRQLRSRYELSLGMHLRDQIALGVTPSKVPHWTAFLSMLIGLFYNKTFRQKLEYLLEQISEVWLLPHWLDLANVEVLAADDTRVPLYMLMVAVHKELDSDDVPDGRFDILLCRDSSREVGE
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what cellular component?
what molecular function?
what biological process?
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what cellular component?
what molecular function?
what biological process?
GO used in curation of literature
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and in integration of databasesMouseEcotope GlyProt
DiabetInGene
GluChem
sphingolipid transporter
activity
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The GO Idea
MouseEcotope GlyProt
DiabetInGene
GluChem
Holliday junction helicase complex
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The GO Idea
MouseEcotope GlyProt
DiabetInGene
GluChem
sphingolipid transporter
activity
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Clark et al., 2005
part_of
is_a
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GO used in reasoning
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GO provides a controlled system of representations for use in
annotating data
• multi-species
• multi-disciplinary
• multi-granularity, from molecules to population
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Gene products involved in cardiac muscle development in humans 19
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$100 mill. invested in literature curation using GO
over 11 million annotations relating gene products described in the UniProt, Ensembl and other databases to terms in the GO
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GO allows a new kind of biological research
based on analysis and comparison of the massive quantities of annotations linking GO terms to the gene products described in scientific literature and in scientific databases
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GO is amazingly successful in overcoming data silo problems
but it covers only
– cellular components
– molecular functions
– biological processes
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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 Compone
nt(FMA, GO)
Cellular Function
(GO)
MOLECULEMolecule
(ChEBI, SO,RnaO, PrO)
Molecular Function(GO)
Molecular Process
(GO)
The Open Biomedical Ontologies (OBO) Foundry23
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The OBO Foundry
– to extend the GO to enable intelligent integration of gigantic bodies of heterogeneous data across the entire domain of the life sciences, including clinical medicine
– to create an evolving, map-like, computable representation of the entire domain of biological and medical reality
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Initial Candidate Members– GO Gene Ontology– CL Cell Ontology– SO Sequence Ontology– ChEBI Chemical Ontology – PATO Phenotype (Quality) Ontology– FMA Foundational Model of Anatomy– ChEBI Chemical Entities of Biological Interest – CARO Common Anatomy Reference Ontology – PRO Protein Ontology 25
The OBO Foundry
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Under development – Disease Ontology– Infectious Disease Ontology– Mammalian Phenotype Ontology – Plant Trait Ontology– Environment Ontology– Ontology for Biomedical Investigations– Behavior Ontology– RNA Ontology – RO Relation Ontology
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The OBO Foundry
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A success story in top-down information integration
Ontologies configured as extensions of a single upper level ontology (BFO)
Used by 100s of researchers to promote interoperability of experimental data in scores of high-throughput domains of biology and medicine via semantic annotation
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The linguistic approach
Bottoms-up, focused on linguistic properties manifested by the contents of a large corpus viewed from a cognitive perspective (mapping/modeling meanings or concepts rather than entities in reality)
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Automatic mining of “assocations” from MEDLINE
FACTA: Finding Associated Concepts with Text Analysis
– What diseases are related to a particular chemical?– What proteins are related to a particular disease?
http://text0.mib.man.ac.uk/software/facta/
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For the linguistic approach
fiction may be no less important than fact
English has no privileged status (the larger the corpus, the better)
consistency (and thus additivity) of annotations is not important, because cognitive perspectives differ
goal is automatic generation of semantic annotations via pattern- matching
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For the scientific approach
factual discourse alone importantEnglish is lingua franca regimentation is allowedgoal of truth: to create a single
computer-processable map of reality via painstaking Handarbeit
truth is one we strive for consistency of annotations
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The linguistic approach is concerned with knowledge representation
The scientific approach is concerned with reality representation
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OBO Relation Ontology (RO 1.0)
Foundational is_apart_of
Spatial located_incontained_inadjacent_to
Temporal transformation_ofderives_frompreceded_by
Participation has_participanthas_agent
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Relation Ontology
supports consistent linkage of OBO Foundry ontologies through a common system of formally defined relations
to enable reasoning both within and across ontologies, and thus also within and between the literature annotated in its terms
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Relation Ontologyinstance_of
is_a (= is a subtype of)
depends_on
part_of
inheres_in
has_input
has_participant
….
http://obofoundry.org/ro/35
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Basic Formal Ontology (BFO)
Continuant Occurrent(Process, Event)
IndependentContinuant
DependentContinuant
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http://ifomis.uni-saarland.de/bfo/
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Fundamental DichotomyContinuants preserve their identity through
change
Occurrents (aka processes)
– have temporal parts
– unfold themselves in successive phases
– exist only in their phases
– have all their parts of necessity
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instance_of
Continuant Occurrent
process, eventIndependentContinuant
thing
DependentContinuant
quality
.... ..... .......
types
instances38
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types vs. instances
compare OWL: T-box vs. A-box
(terminology vs. assertions)
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3 kinds of (binary) relations
Between types
• human is_a mammal
• human heart part_of human
Between an instance and a type
• this human instance_of the type human
• this human allergic_to the type tamiflu
Between instances
• Mary’s heart part_of Mary
• Mary’s aorta connected_to Mary’s heart40
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depends_on
Continuant Occurrent
process, eventIndependentContinuant
thing
DependentContinuant
quality
.... ..... .......quality dependson bearer
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Dependent continuants
the whiteness quality of this cheese
your role as lecturer
the disposition of this peach to ripen
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depends_on
Continuant Occurrent
process
IndependentContinuant
thing
DependentContinuant
quality
.... ..... .......temperature dependson bearer
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depends_on
Continuant Occurrent
process, eventIndependentContinuant
thing
DependentContinuant
quality, …
.... ..... .......event dependson participant
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Type-level relations presuppose the underlying instance-level relations
A is_a B =def. A and B are types and all instances of A are instances of B
A part_of B =def. All instances of A are instance-level-parts-of some instance of B
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The assertions linking terms in ontologies must hold universally
Hence all type-level relations in RO
are provided with
All-Some definitions
(For linguists, Some-Some relations
are equally important)
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Including only All-Some relations means:
All relations evaluable as
1. Transitive
2. Symmetric
3. Reflexive
4. Anti-Symmetric
All relations support logical reasoning
– as contrasted with: is_related_to, is_associated_with, is_narrower_in_meaning_than …
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Reasoning should be able to cascade from one relational assertion (A R1 B) to the next (B R2 C).
Find all DNA binding proteins should also Find all transcription factor proteins because
– Transcription factor is_a DNA binding protein
Only the All-Some structure guarantees such cascading of relational assertions
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Organisms are continuantsthey are entities which endure through time through gain and loss of parts
Processes are occurrents
they are entities which unfold through time, and have all their parts as a matter of necessity
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human testis part_of adult human being
but nothuman being has_part human testis
and not even
male human being has_part human testis
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part_of for continuant types
A part_of B =def.
For all x, t if x instance_of A at t then there is some y, y instance_of B at t and x instance_level_part_of y at t
cell membrane part_of cell55
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part_of for occurrent types
A part_of B =def.
For all x, if x instance_of A then there is some y, y instance_of B and x instance_level_part_of y
EVERY A IS PART OF SOME B 56
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transformation_of
A transformation_of B =Def.
Every instance of A was at some earlier time an instance of B
– adult transformation_of child
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transformation_of
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c at t1
C
c at t
C1
time
same instance
pre-RNA mature RNA
adultchild
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C
c at t
C1
c1 at t1
C'
c' at t
time
instances
zygote derives_fromovumsperm
derives_from
correction to original Genome Biology paper: derivation is never one-to-one 61
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two continuants fuse to form a new continuant
C
c at t
C1
c1 at t1
C'
c' at t fusion
derives_from
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one initial continuant is replaced by two successor continuants
C
c at t
C1
c1 at t1
C2
c1 at t1
fission
derives_from
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one continuant detaches itself from an initial continuant, which itself continues to exist
C
c at t c at t1
C1
c1 at t
budding
derives_from combined with transformation_of
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one continuant absorbs a second continuant while itself continuing to exist
C
c at t
c at t1
C'
c' at t capture
derives_from combined with transformation_of
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ISO “Concept logic” for mereology
Toronto part_of Ontario
brain part_of central nervous system
ISO, “Guidelines for the Construction, Format, and Management of Monolingual Controlled Vocabularies” ANSI/NISO Z39.19-2005) sees these as examples of the same part_of relation
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Instances vs. types
Instance-level relations and type-level relations have logically distinct properties
Type relations are liftings of instance relations
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What is symmetric on the level of instances need not be symmetric on the level of types
adjacency on the instance level is always symmetric
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Not however on the level of types:
seminal vesicle adjacent_to urinary bladder
Not: urinary bladder adjacent_to seminal vesicle
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Similarly, on the level of types, while:
nucleus adjacent_to cytoplasm
it is not the case that
cytoplasm adjacent_to nucleus
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continuous_with on the instance level is always symmetric
a continuous_with b on the instance level means: there is a fiat boundary
between a and b
if a continuous_with b,
then b continuous_with a
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continuous_with as a relation between types
A continuous_with B =Def.
for all x, if x instance-of A then there is some y such that y instance_of B and x continuous_with y
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continuous_with is not symmetric
Consider lymph node and lymphatic vessel
Each lymph node is continuous with some lymphatic vessel, but there are lymphatic vessels (e.g. lymphs and lymphatic trunks) which are not continuous with any lymph nodes
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3 kinds of binary relations
Between types• human is_a mammal• cell nucleus part_of cell
Between an instance and a type• this human instance_of the type human• this human allergic_to the type penicillin
Between instances• Mary’s heart part_of Mary• Mary’s aorta connected_to Mary’s heart
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Linguistic vs. scientific approach to semantic annotation
Semantic annotation can provide support for logical reasoning across the content of scientific literature only if the distinctions between relations at the type level and relations at the instance level are taken account of.
(Many?) linguistic accounts of relations do not take account of this distinction.
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Why not?
Because linguistic accounts (like dictionaries) focus on relations between meanings, not on instances in reality
Because linguistic accounts focus on what is meaningfully combinable, rather than on what is logically inferrable
Because linguistic accounts focus on relations captured grammatically, not on relations observed experimentally and captured in scientific theories
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The Relation Ontology
Barry Smith
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Sophia AnaniadouUK National Centre for Text Mining
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Do linguistics and biology truly ever meet?