ontology and the future of biomedical research barry smith
Post on 19-Dec-2015
217 views
TRANSCRIPT
![Page 1: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/1.jpg)
Ontology and the Future of Biomedical Research
Barry Smithhttp://ifomis.org
![Page 2: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/2.jpg)
Institute for Formal Ontology and Medical Information Science
Saarland University
![Page 3: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/3.jpg)
From chromosome
to disease
![Page 4: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/4.jpg)
Problem:how to reason with data deriving from different sources, each of which uses its own system of classification ?
![Page 5: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/5.jpg)
Solution:
Ontology !
![Page 6: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/6.jpg)
Examples of current needs for ontologies in biomedicine
– to enforce semantic consistency within a database
– to enable data sharing and re-use– to enable data integration (bridging
across data at multiple granularities)
– to allow querying
![Page 7: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/7.jpg)
What is needed
strong general purpose classification hierarchies created by domain specialists clear, rigorous definitionsthoroughly tested in real use casesupdated in light of scientific advance
![Page 8: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/8.jpg)
The actuality (too often)
myriad special purpose ‘light’ ontologies, prepared by ontology engineers and deposited in internet ‘repositories’ or ‘registries’
![Page 9: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/9.jpg)
ontologies for ‘agent’
![Page 10: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/10.jpg)
![Page 11: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/11.jpg)
General trend
on the part of NIH, FDA and other bodies to consolidate ontology-based standards for the communication and processing of biomedical data.
![Page 12: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/12.jpg)
Responses to this trend
Old: UMLS (Unified Medical Language System) – rooted in the faithfulness to the ways language is used by different medical communities
![Page 13: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/13.jpg)
SNOMED
DEMONS
U M L S
![Page 14: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/14.jpg)
– congenital absent nipple is_a nipple– cancer documentation is_a cancer– disease prevention is_a disease– repair and maintenance of wheelchair is_a
disease– water is_a nursing phenomenon– part-whole =def. a nursing phenomenon with
topology part-whole
U M L S
![Page 15: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/15.jpg)
MeSH
MeSH Descriptors Index Medicus Descriptor Anthropology, Education, Sociology and Social Phenomena (MeSH Category) Social Sciences Political Systems National Socialism
![Page 16: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/16.jpg)
MeSH
National Socialism is_a Political SystemsNational Socialism is_a Anthropology ...National Socialism is_a Social SciencesNational Socialism is_a MeSH Descriptors
![Page 17: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/17.jpg)
New: Semantic Web deposits
Pet Profile Ontology
Review Vocabulary
Band Description Vocabulary
Musical Baton Vocabulary
MusicBrainz Metadata Vocabulary
Kissology
![Page 18: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/18.jpg)
http://www.w3.org/
Beer Ontology
all instances of hops that have ever existed are necessarily ingredients of beer.
![Page 19: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/19.jpg)
some nice computational resources, but low expressivityand few genuinely scientific demonstration cases
OWL-based ontologies …
![Page 20: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/20.jpg)
OWL’s syntactic regimentation is not enough to ensure high-quality
ontologies
– the use of a common syntax and logical machinery and the careful separating out of ontologies into namespaces does not solve the problem of ontology integration
![Page 21: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/21.jpg)
Both UMLS- and OWL-type responses involve ad hoc creation of new terminologies by each community
Many of these terminologies remain as torsos, gather dust, poison the wells, ...
![Page 22: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/22.jpg)
How to do better?How to create the conditions for a step-by-step evolution towards high quality ontologies in the biomedical domainwhich will serve as stable attractors for clinical and biomedical researchers in the future?
![Page 23: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/23.jpg)
A basic distinction
type vs. instance
science text vs. clinical document
dog vs. Fido
![Page 24: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/24.jpg)
Instances are not represented in an ontology built for
scientific purposesIt is the generalizations that are
important
(but instances must still be taken into account)
![Page 25: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/25.jpg)
A 515287 DC3300 Dust Collector Fan
B 521683 Gilmer Belt
C 521682 Motor Drive Belt
Catalog vs. inventory
![Page 26: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/26.jpg)
Ontology Types Instances
![Page 27: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/27.jpg)
Ontology = A Representation of Types
![Page 28: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/28.jpg)
Ontology = A Representation of Types
Each node of an ontology consists of:
• preferred term (aka term)
• term identifier (TUI, aka CUI)
• synonyms
• definition, glosses, comments
![Page 29: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/29.jpg)
Each term in an ontology represents exactly one type
hence ontology terms should be singular nouns
National Socialism is_a Political Systems
![Page 30: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/30.jpg)
An ontology is a representation of types
We learn about types in reality from looking at the results of scientific experiments in the form of scientific theories – which describe not what is particular in reality but rather what is general
Ontologies need to exploit the evolutionary path to convergence created by science
![Page 31: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/31.jpg)
High quality shared ontologies build communities
NIH, FDA trend to consolidate ontology-based standards for the communication and processing of biomedical data.
caBIG / NECTAR / BIRN / BRIDG ...
![Page 32: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/32.jpg)
http://obo.sourceforge.net
![Page 33: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/33.jpg)
http://www.geneontology.org/
![Page 34: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/34.jpg)
![Page 35: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/35.jpg)
![Page 36: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/36.jpg)
The Methodology of Annotations
GO employs scientific curators, who use experimental observations reported in the biomedical literature to link gene products with GO terms in annotations.
This gene product exercises this function, in this part of the cell, leading to these biological processes
![Page 37: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/37.jpg)
The Methodology of Annotations
This process of annotating literature leads to improvements and extensions of the ontology, which in turn leads to better annotations
This institutes a virtuous cycle of improvement in the quality and reach of both future annotations and the ontology itself.
Annotations + ontology taken together yield a slowly growing computer-interpretable map of biological reality.
![Page 38: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/38.jpg)
The OBO The OBO FoundryFoundry
![Page 39: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/39.jpg)
A subset of OBO ontologies, whose developers have agreed in advance to accept a common set of principles designed to ensure
– intelligibility to biologists (curators, annotators, users)
– formal robustness – stability– compatibility– interoperability – support for logic-based reasoning
The OBO FoundryThe OBO Foundry
![Page 40: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/40.jpg)
Custodians
•Michael Ashburner (Cambridge)•Suzanna Lewis (Berkeley)•Barry Smith (Buffalo/Saarbrücken)
The OBO FoundryThe OBO Foundry
![Page 41: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/41.jpg)
A collaborative experiment
participants have agreed in advance to a growing set of principles specifying best practices in ontology developmentdesigned to guarantee interoperability of ontologies from the very start
The OBO FoundryThe OBO Foundry
![Page 42: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/42.jpg)
The developers of each ontology commit to its maintenance in light of scientific advance, and to soliciting community feedback for its improvement. They commit to working with other Foundry members to ensure that, for any particular domain, there is community convergence on a single reference ontology.
The OBO FoundryThe OBO Foundry
![Page 43: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/43.jpg)
Initial Candidate Members of the OBO Foundry
– GO Gene Ontology– CL Cell Ontology– SO Sequence Ontology– ChEBI Chemical Ontology – PATO Phenotype Ontology– FuGO Functional Genomics Investigation
Ontology– FMA Foundational Model of Anatomy– RO Relation Ontology
The OBO FoundryThe OBO Foundry
![Page 44: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/44.jpg)
Under development – Disease Ontology– NCI Thesaurus– Mammalian Phenotype Ontology – OBO-UBO / Ontology of Biomedical Reality – Organism (Species) Ontology– Plant Trait Ontology– Protein Ontology– RnaO RNA Ontology
The OBO FoundryThe OBO Foundry
![Page 45: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/45.jpg)
Considered for development
– Environment Ontology– Behavior Ontology– Biomedical Image Ontology– Clinical Trial Ontology
The OBO FoundryThe OBO Foundry
![Page 46: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/46.jpg)
CRITERIA
The OBO FoundryThe OBO FoundryThe OBO FoundryThe OBO Foundry
The ontology is open and available to be used by all.
The developers of the ontology agree in advance to collaborate with developers of other OBO Foundry ontology where domains overlap.
The ontology is in, or can be instantiated in, a common formal language.
![Page 47: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/47.jpg)
The ontology possesses a unique identifier space within OBO.
The ontology provider has procedures for identifying distinct successive versions.
The ontology includes textual definitions for all terms.
CRITERIA
The OBO FoundryThe OBO Foundry
![Page 48: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/48.jpg)
The ontology has a clearly specified and clearly delineated content.
The ontology is well-documented.
The ontology has a plurality of independent users.
CRITERIA
The OBO FoundryThe OBO Foundry
![Page 49: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/49.jpg)
The ontology uses relations which are unambiguously defined following the pattern of definitions laid down in the OBO Relation Ontology.*
*Genome Biology 2005, 6:R46
CRITERIA
The OBO FoundryThe OBO Foundry
![Page 50: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/50.jpg)
CRITERIA
Further criteria will be added over time in order to bring about a gradual improvement in the quality of the ontologies in the Foundry
The OBO FoundryThe OBO FoundryThe OBO FoundryThe OBO Foundry
![Page 51: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/51.jpg)
A reference ontology
is analogous to a scientific theory; it seeks to optimize representational adequacy to its subject matter to the maximal degree that is compatible with the constraints of computational usefulness.
![Page 52: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/52.jpg)
An application ontology
is comparable to an engineering artifact such as a software tool. It is constructed for a specific practical purpose.Examples:
National Cancer Institute Thesaurus FuGO Functional Genomics
Investigation Ontology
![Page 53: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/53.jpg)
Reference Ontology vs. Application Ontology
Currently, application ontologies are often built afresh for each new task; commonly introducing not only idiosyncrasies of format or logic, but also simplifications or distortions of their subject-matters. To solve this problem application ontology development should take place always against the background of a formally robust reference ontology framework
![Page 54: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/54.jpg)
Advantages of the methodology of shared coherently defined
ontologies• promotes quality assurance (better
coding)• guarantees automatic reasoning across
ontologies and across data at different granularities
• yields direct connection to temporally indexed instance data
![Page 55: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/55.jpg)
Advantages of the methodology of shared coherently defined
ontologies
We know that high-quality ontologies can help in creating better mappings e.g. between human and model organism phenotypes
S Zhang, O Bodenreider, “Alignment of Multiple Ontologies of Anatomy: Deriving Indirect Mappings from Direct Mappings to a Reference Ontology”, AMIA 2005
![Page 56: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/56.jpg)
Advantages of the methodology of shared coherently defined ontologies
once the interoperable gold standard reference ontologies are there, it will make sense to reformulate parts of existing incompatible terminologies (e.g. in UMLS) in terms of the standard ontologies in order to achieve greater domain coverage and alignment of different but veridical views. Thus not everything that was done in the past turns out to be a waste.
![Page 57: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/57.jpg)
Goal: to create a family of gold standard reference ontologies upon which terminologies developed for specific applications can draw
The OBO FoundryThe OBO Foundry
![Page 58: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/58.jpg)
Goal: to introduce the scientific method into ontology development:– all Foundry ontologies must be constantly
updated in light of scientific advance– all Foundry ontology developers must work
with all other Foundry ontology developers in a spirit of scientific collaboration
The OBO FoundryThe OBO Foundry
![Page 59: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/59.jpg)
Goal: to replace the current policy of ad hoc
creation of new database schemas by each clinical research group by providing reference ontologies in terms of which database schemas can be defined
The OBO FoundryThe OBO Foundry
![Page 60: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/60.jpg)
Goal: to introduce some of the features of scientific peer review into biomedical ontology development
The OBO FoundryThe OBO Foundry
![Page 61: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/61.jpg)
Goal:to create controlled vocabularies for use by clinical trial banks, clinical guidelines bodies, scientific journals, ...
The OBO FoundryThe OBO Foundry
![Page 62: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/62.jpg)
Goal:to create controlled vocabularies for use by clinical trial banks, clinical guidelines bodies, scientific journals, ...
The OBO FoundryThe OBO Foundry
![Page 63: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/63.jpg)
Goal:to create an evolving map-like representation of the entire domain of biological reality
The OBO FoundryThe OBO Foundry
![Page 64: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/64.jpg)
GO’s three ontologies
molecular function
cellular component
biological process
![Page 65: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/65.jpg)
cell (types)
molecular function
(GO)
species
molecular process
cellular anatom
y
anatomy(fly, fish,
human...)
cellularphysiology
organism-levelphysiology
ChEBI,Sequence,
RNA ...
![Page 66: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/66.jpg)
cell (types)
molecular function
(GO)
species
molecular process
cellular anatom
y
anatomy(fly, fish, human...)
cellularphysiology
organism-levelphysiology
ChEBI,Sequence,
RNA ...
normal(functionings)
![Page 67: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/67.jpg)
pathophysiology(disease)
pathoanatomy(fly, fish, human ...)
pathological(malfunctionings)
![Page 68: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/68.jpg)
cell (types)
molecular function
(GO)
species
molecular process
cellular anatom
y(GO)
anatomy(fly, fish, human...)
cellularphysiology
organism-levelphysiology
ChEBI,Sequence,
RNA ...
pathophysiology(disease)
pathoanatomy(fly, fish, human ...)
![Page 69: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/69.jpg)
cell (types)
molecular function
(GO)
species
molecular process
cellular anatom
y
anatomy(fly, fish, human...)
cellularphysiology
organism-levelphysiology
ChEBI,Sequence,
RNA ...
pathophysiology(disease)
pathoanatomy(fly, fish, human ...)
phenotype
![Page 70: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/70.jpg)
cell (types)
molecular function
(GO)
species
molecular process
cellular anatom
y
anatomy(fly, fish, human...)
cellularphysiology
organism-levelphysiology
ChEBI,Sequence,
RNA ...
pathophysiology(disease)
pathoanatomy(fly, fish, human ...)
phenotype
investigation(FuGO)
![Page 71: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/71.jpg)
Ende
![Page 72: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/72.jpg)
First step
Alignment of OBO Foundry ontologies through a common system of formally defined relations in the OBO Relation Ontology
See “Relations in Biomedical Ontologies”, Genome Biology Apr. 2005
![Page 73: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/73.jpg)
Judith Blake:
“The use of bio-ontologies … ensures consistency of data curation, supports extensive data integration, and enables robust exchange of information between heterogeneous informatics systems. .. ontologies … formally define relationships between the concepts.”
![Page 74: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/74.jpg)
"Gene Ontology: Tool for the Unification of Biology"
an ontology "comprises a set of well-defined terms with well-defined relationships" (Ashburner et al., 2000, p. 27)
![Page 75: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/75.jpg)
is_a (sensu UMLS)A is_a B =def
‘A ’ is narrower in meaning than ‘B ’
grows out of the heritage of dictionaries
(which ignore the basic distinction between types and instances)
![Page 76: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/76.jpg)
is_acongenital absent nipple is_a nipplecancer documentation is_a cancerdisease prevention is_a diseaseNazism is_a social science
![Page 77: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/77.jpg)
is_a (sensu logic)A is_a B =def
For all x, if x instance_of A then x instance_of B
cell division is_a biological process
adult is_a child ???
![Page 78: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/78.jpg)
Two kinds of entitiesoccurrents (processes, events,
happenings)cell division, ovulation, death
continuants (objects, qualities, ...)cell, ovum, organism, temperature of organism, ...
![Page 79: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/79.jpg)
is_a (for occurrents)A is_a B =def
For all x, if x instance_of A then x instance_of B
cell division is_a biological process
![Page 80: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/80.jpg)
is_a (for continuants)A is_a B =def
For all x, t if x instance_of A at t then x instance_of B at t
abnormal cell is_a celladult human is_a humanbut not: adult is_a child
![Page 81: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/81.jpg)
Part_of as a relation between types is more problematic than is standardly supposed
heart part_of human being ?human heart part_of human being ?human being has_part human testis ?human testis part_of human being ?
![Page 82: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/82.jpg)
two kinds of parthood
1. between instances:Mary’s heart part_of Marythis nucleus part_of this cell
2. between typeshuman heart part_of humancell nucleus part_of cell
![Page 83: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/83.jpg)
Definition of part_of as a relation between types
A part_of B =Def all instances of A are instance-level parts of some instance of B
ALL–SOME STRUCTURE
![Page 84: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/84.jpg)
part_of (for occurrents)A part_of B =Def
For all x, if x instance_of A then there is some y, y instance_of B and x part_of ywhere ‘part_of’ is the instance-level part relation
![Page 85: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/85.jpg)
part_of (for continuants)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 part_of y
where ‘part_of’ is the instance-level part relation
ALL-SOME STRUCTURE
![Page 86: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/86.jpg)
How to use the OBO Relation OntologyOntologies are representations of types and
of the relations between typesThe definitions of these relations involve
reference to times and instances, but these references are washed out when we get to the assertions (edges) in the ontology
But curators should still be aware of the underlying definitions when formulating such assertions
![Page 87: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/87.jpg)
part_of (for occurrents)A part_of B =Def
For all x, if x instance_of A then there is some y, y instance_of B and x part_of ywhere ‘part_of’ is the instance-level part relation
![Page 88: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/88.jpg)
A part_of B, B part_of C ...The all-some structure of such
definitions allowscascading of inferences (true path
rule)(i) within ontologies(ii) between ontologies(iii) between ontologies and repositories of instance-data
![Page 89: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/89.jpg)
Strengthened true path ruleWhichever A you choose, the instance of
B of which it is a part will be included in some C, which will include as part also the A with which you began
The same principle applies to the other relations in the OBO-RO:
located_at, transformation_of, derived_from, adjacent_to, etc.
![Page 90: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/90.jpg)
Kinds of relationsBetween types:
– is_a, part_of, ...
Between an instance and a type– this explosion instance_of the type
explosion
Between instances:– Mary’s heart part_of Mary
![Page 91: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/91.jpg)
In every ontologysome terms and some relations are primitive = they cannot be defined (on pain of infinite regress)
Examples of primitive relations:– identity– instantiation– (instance-level) part_of– (instance-level)
continuous_with
![Page 92: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/92.jpg)
Fiat and bona fide boundaries
![Page 93: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/93.jpg)
Continuity
Attachment
Adjacency
![Page 94: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/94.jpg)
everything here is an independent continuant
![Page 95: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/95.jpg)
structures vs. formations = bona fide vs. fiat boundaries
![Page 96: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/96.jpg)
Modes of Connection
The body is a highly connected entity.
Exceptions: cells floating free in blood.
![Page 97: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/97.jpg)
Modes of Connection
Modes of connection:attached_to (muscle to bone) synapsed_with (nerve to nerve, nerve to muscle)
continuous_with (= share a fiat boundary)
![Page 98: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/98.jpg)
articular eminencearticular (glenoid)fossa
ANTERIOR
Attachment, location, containment
![Page 99: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/99.jpg)
Containment involves relation to a hole or cavity
1: cavity2: tunnel, conduit (artery)3: mouth; a snail’s shell
![Page 100: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/100.jpg)
Fiat vs. Bona Fide Boundaries
Fiat boundary Physical boundary
![Page 101: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/101.jpg)
Double Hole Structure
Medium (filling the environing hole)
Tenant (occupying the central hole)
Retainer (a boundary of some surrounding structure)
![Page 102: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/102.jpg)
head of condyle
neck of condyle
fossa
fiat boundary
THE TEMPOROMANDIBULAR JOINTTHE TEMPOROMANDIBULAR JOINT
![Page 103: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/103.jpg)
continuous_with(a relation between instances which
share a fiat boundary)
is always symmetric:
if x continuous_with y , then y continuous_with x
![Page 104: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/104.jpg)
continuous_with(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
![Page 105: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/105.jpg)
continuous_with is not always 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
![Page 106: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/106.jpg)
Adjacent_toas a relation between types
is not symmetric
Considerseminal vesicle adjacent_to urinary bladder
Not: urinary bladder adjacent_to seminal vesicle
![Page 107: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/107.jpg)
instance levelthis nucleus is adjacent to this
cytoplasmimplies:
this cytoplasm is adjacent to this nucleus
type levelnucleus adjacent_to cytoplasmNot: cytoplasm adjacent_to nucleus
![Page 108: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/108.jpg)
ApplicationsExpectations of symmetry e.g. for
protein-protein interactions may hold only at the instance level
if A interacts with B, it does not follow that B interacts with A
if A is expressed simultaneously with B, it does not follow that B is expressed simultaneously with A
![Page 109: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/109.jpg)
c at t1
C
c at t
C1
time
same instance
transformation_of
pre-RNA mature RNA
adultchild
![Page 110: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/110.jpg)
transformation_of
A transformation_of B =Def. Every instance of A was at some earlier time an instance of B
adult transformation_of child
![Page 111: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/111.jpg)
C
c at t c at t1
C1
tumor development
![Page 112: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/112.jpg)
C
c at t
C1
c1 at t1
C'
c' at t
time
instances
zygote derives_fromovumsperm
derives_from
![Page 113: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/113.jpg)
two continuants fuse to form a new continuant
C
c at t
C1
c1 at t1
C'
c' at t fusion
![Page 114: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/114.jpg)
one initial continuant is replaced by two successor continuants
C
c at t
C1
c1 at t1
C2
c1 at t1
fission
![Page 115: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/115.jpg)
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
![Page 116: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/116.jpg)
one continuant absorbs a second continuant while itself continuing to exist
C
c at t
c at t1
C'
c' at t capture
![Page 117: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/117.jpg)
A suite of defined relations between typesFoundation
al is_apart_of
Spatial located_incontained_inadjacent_to
Temporal transformation_ofderives_frompreceded_by
Participation
has_participanthas_agent
![Page 118: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/118.jpg)
To be added to the Relation Ontology
lacks (between an instance and a type, e.g. this fly lacks wings)
dependent_on (between a dependent entity and its carrier or bearer)
quality_of (between a dependent and an independent continuant)
functioning_of (between a process and an independent continuant)
![Page 119: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/119.jpg)
Low Hanging Fruit
Ontologies should include only those relational assertions which hold universally (= have the ALL-SOME form)
Often, order will matter here:We can include
adult transformation_of childbut not
child transforms_into adult
![Page 120: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/120.jpg)
The Gene Ontology
![Page 121: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/121.jpg)
GO’s three ontologies
molecular functions
cellular components
biological processes
![Page 122: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/122.jpg)
When a gene is identified
three types of questions need to be addressed:
1. Where is it located in the cell? 2. What functions does it have on the
molecular level? 3. To what biological processes do these
functions contribute?
![Page 123: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/123.jpg)
Three granularities:
Cellular (for components)Molecular (for functions)Organ + organism (for processes)
![Page 124: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/124.jpg)
GO has cells
but it does not include terms for molecules or organisms within any of its three ontologiesexcept e.g. GO:0018995 host=Def. Any organism in which another organism spends part or all of its life cycle
![Page 125: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/125.jpg)
Are the relations between functions and processes a matter of granularity?
Molecular activities are the ‘building blocks’ of biological processes ?
But they are not allowed to be represented in GO as parts of biological processes
![Page 126: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/126.jpg)
GO’s three ontologies
molecular functions
cellular components
biological processes
![Page 127: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/127.jpg)
What does “function” mean?
an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to the organism’s survival
the function is this disposition
![Page 128: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/128.jpg)
Improved version
an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to the organism’s realization of the canonical life plan for an organism of that type
![Page 129: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/129.jpg)
This canonical life plan might include
canonical embryological development
canonical growthcanonical reproductioncanonical agingcanonical death
![Page 130: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/130.jpg)
The function of the heart is to pump blood
Not every activity (process) in an organism is the exercise of a function – there are – mal functionings– side-effects (heart beating)– accidents (external
interference)– background stochastic activity
![Page 131: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/131.jpg)
Kidney
![Page 132: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/132.jpg)
Nephron
![Page 133: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/133.jpg)
Functional Segments
![Page 134: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/134.jpg)
Functions
![Page 135: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/135.jpg)
FunctionsThis is a screwdriverThis is a good screwdriverThis is a broken screwdriver
This is a heartThis is a healthy heartThis is an unhealthy heart
![Page 136: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/136.jpg)
Functions are associated with certain characteristic process shapes
Screwdriver: rotates and simultaneously moves forward simultaneously transferring torque from hand and arm to screw
Heart: performs a contracting movement inwards and an expanding movement outwards
![Page 137: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/137.jpg)
Not functioning at all
leads to death, modulo internal factors:
plasticity redundancy (2 kidneys)criticality of the system involved
external factors:prosthesis (dialysis machines, oxygen tent)special environmentsassistance from other organisms
![Page 138: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/138.jpg)
What clinical medicine is for
to eliminate malfunctioning by fixing broken body parts(or to prevent the appearance of malfunctioning by intervening e.g. at the molecular level)
![Page 139: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/139.jpg)
Hypothesis: there are no ‘bad’ functions
It is not the function of an oncogene to cause cancer Oncogenes were in every case proto-oncogenes with functions of their ownThey become oncogenes because of bad (non-prototypical) environments
![Page 140: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/140.jpg)
Is there an exception for molecular functions?
Does this apply only to functions on biological levels of granularity
(= levels of granularity coarser than the molecule) ?
If pathology is the deviation from (normal) functioning, does it make sense to talk of a pathological molecule?
(Pathologically functioning molecule vs. pathologically structured molecule)
![Page 141: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/141.jpg)
Is there an exception for molecular functions?
A molecular function is a propensity of a gene product instance to perform actions on the molecular level of granularity. Hypothesis 1: these actions must be reliably such as to contribute to biological processes.Hypothesis 2: these actions must be reliably such as to contribute to the organism’s realization of the canonical life plan for an organism of that type.
![Page 142: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/142.jpg)
The Gene Ontology
is a canonical ontology – it represents only what is normal in the realm of molecular functioning
![Page 143: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/143.jpg)
The GO is a canonical representation
“The Gene Ontology is a computational representation of the ways in which gene products normally function in the biological realm”
Nucl. Acids Res. 2006: 34.
![Page 144: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/144.jpg)
The FMA is a canonical representation
It is a computational representation of types and relations between types deduced from the qualitative observations of the normal human body, which have been refined and sanctioned by successive generations of anatomists and presented in textbooks and atlases of structural anatomy.
![Page 145: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/145.jpg)
The importance of pathways (successive causality)
Each stage in the history of a disease presupposes the earlier stages
Therefore need to reason across time, tracking the order of events in time, using relations such as derives_from, transformation_of ...
Need pathway ontologies on every level of granularity
![Page 146: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/146.jpg)
The importance of granularity (simultaneous causality)
Networks are continuantsAt any given time there are networks existing
in the organism at different levels of granularity
Changes in one cause simultaneous changes in all the others
(Compare Boyle’s law: a rise in temperature causes a simultaneous increase in pressure)
![Page 147: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/147.jpg)
The Granularity Gulf
most existing data-sources are of fixed, single granularity
many (all?) clinical phenomena cross granularities
Therefore need to reason across time, tracking the order of events in time
![Page 148: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/148.jpg)
Good ontologies require:
consistent use of terms, supported by logically coherent (non-circular) definitions, in equivalent human-readable and computable formats
coherent shared treatment of relations to allow cascading inference both within and between ontologies
![Page 149: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/149.jpg)
Three fundamental dichotomies
• continuants vs. occurrents• dependent vs. independent • types vs. instances
![Page 150: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/150.jpg)
ONTOLOGIES AREREPRESENTATIONS OF TYPES
aka kinds, universals, categories, species, genera, ...
![Page 151: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/151.jpg)
Continuants (aka endurants)– have continuous existence in time– preserve their identity through
change– exist in toto whenever they exist at
all
Occurrents (aka processes)– have temporal parts– unfold themselves in successive
phases– exist only in their phases
![Page 152: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/152.jpg)
You are a continuant
Your life is an occurrent
You are 3-dimensional
Your life is 4-dimensional
![Page 153: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/153.jpg)
Dependent entities
require independent continuants as their bearers
There is no run without a runnerThere is no grin without a cat
![Page 154: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/154.jpg)
Dependent vs. independent continuants
Independent continuants (organisms, cells, molecules, environments)
Dependent continuants (qualities, shapes, roles, propensities, functions)
![Page 155: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/155.jpg)
All occurrents are dependent entities
They are dependent on those independent continuants which are their participants (agents, patients, media ...)
![Page 156: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/156.jpg)
Top-Level Ontology
ContinuantOccurrent
(always dependent on one or more
independent continuants)
IndependentContinuant
DependentContinuant
![Page 157: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/157.jpg)
= A representation of top-level types
Continuant Occurrent
IndependentContinuant
DependentContinuant
cell component
biological process
molecular function
![Page 158: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/158.jpg)
Top-Level Ontology
Continuant Occurrent
IndependentContinuant
DependentContinuant
Functioning
Side-Effect, Stochastic Process, ...
Function
![Page 159: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/159.jpg)
Top-Level OntologyContinuant Occurrent
IndependentContinuant
DependentContinuant
Functioning Side-Effect, Stochastic Process, ...
Function
![Page 160: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/160.jpg)
Top-Level OntologyContinuant Occurrent
IndependentContinuant
DependentContinuant
Quality Function Spatial Region
Functioning Side-Effect, Stochastic Process, ...
instances (in space and time)
![Page 161: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/161.jpg)
Smith B, Ceusters W, Kumar A, Rosse C. On Carcinomas and Other Pathological Entities, Comp Functional Genomics, Apr. 2006
![Page 162: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/162.jpg)
everything here is an independent continuant
![Page 163: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/163.jpg)
Functions, etc.
Some dependent continuants are realizable
expression of a geneapplication of a therapycourse of a diseaseexecution of an algorithmrealization of a protocol
![Page 164: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/164.jpg)
Functions vs Functionings
the function of your heart = to pump blood in your body
this function is realized in processes of pumping blood
not all functions are realized (consider the function of this sperm ...)
![Page 165: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/165.jpg)
Concepts
Biomedical ontology integration will never be achieved through integration of meanings or concepts
The problem is precisely that different user communities use different concepts
Concepts are in your head and will change as your understanding changes
![Page 166: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/166.jpg)
ConceptsOntologies represent types: not
concepts, meanings, ideas ...Types exist, with their instances, in
objective reality– including types of image, of imaging
process, of brain region, of clinical procedure, etc.
![Page 167: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/167.jpg)
Rules on typesDon’t confuse types with wordsDon’t confuse types with conceptsDon’t confuse types with ways of
getting to know typesDon’t confuse types with ways of
talking about typesDon’t confuses types with data about
types
![Page 168: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/168.jpg)
Some other simple rules for high quality ontologies
![Page 169: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/169.jpg)
Univocity Terms should have the same meanings
on every occasion of use.They should refer to the same kinds of
entities in realityBasic ontological relations such as is_a
and part_of should be used in the same way by all ontologies
![Page 170: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/170.jpg)
Positivity
Complements of types are not themselves types. Hence terms such as
non-mammal non-membrane other metalworker in New Zealand
do not designate types in reality
![Page 171: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/171.jpg)
Ontology of types logic of termsThere are no conjunctive and
disjunctive types:
anatomic structure, system, or substance
musculoskeletal and connective tissue disorder
rheumatism, excluding the back
![Page 172: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/172.jpg)
ObjectivityWhich types exist in reality is not a
function of our knowledge.Terms such as
unknownunclassifiedunlocalizedarthropathies not otherwise specified
do not designate types in reality.
![Page 173: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/173.jpg)
Keep Epistemology Separate from OntologyIf you want to say that
We do not know where A’s are located
do not invent a new class of A’s with unknown locations(A well-constructed ontology should grow linearly; it should not need to delete classes or relations because of increases in knowledge)
![Page 174: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/174.jpg)
Syntactic SeparatenessDo not confuse sentences with terms
If you want to say
I surmise that this is a case of pneumonia
do not invent a new class of surmised pneumonias
![Page 175: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/175.jpg)
Single Inheritance
No kind in a classificatory hierarchy should have more than one is_a parent on the immediate higher level
![Page 176: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/176.jpg)
Multiple Inheritance
thing
car
blue thing
blue car
is_a is_a
![Page 177: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/177.jpg)
Multiple Inheritance
is a source of errorsencourages lazinessserves as obstacle to integration with
neighboring ontologieshampers use of Aristotelian methodology
for defining terms
![Page 178: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/178.jpg)
Multiple Inheritance
thing
car
blue thing
blue car
is_a1 is_a2
![Page 179: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/179.jpg)
is_a Overloading
The success of ontology alignment demands that ontological relations (is_a, part_of, ...) have the same meanings in the different ontologies to be aligned.
![Page 180: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/180.jpg)
Example: is_a is pressed into service by the GO to express location
is-located-at and similar relations are expressed by creating special compound terms using:
site of …… within …… in …extrinsic to …
yielding associated errors
![Page 181: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/181.jpg)
e.g. errors with ‘within’lytic vacuole within a protein storage
vacuole
lytic vacuole within a protein storage vacuole is-a protein storage vacuole
Compare:embryo within a uterus is-a uterus
![Page 182: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/182.jpg)
similar problems with part_of
extrinsic to membrane part_of membrane
![Page 183: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/183.jpg)
CompositionalityThe meanings of compound terms
should be determined 1. by the meanings of component terms
together with2. the rules governing syntax
![Page 184: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/184.jpg)
Why do we need rules/standards for good ontology?
Ontologies must be intelligible both to humans (for annotation and curation) and to machines (for reasoning and error-checking): the lack of rules for classification leads to human error and blocks automatic reasoning and error-checking
Intuitive rules facilitate training of curators and annotators
Common rules allow alignment with other ontologies
![Page 185: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/185.jpg)
When we annotate the record of an experiment
we use terms representing types to capture what we learn about:– this experiment (instance), performed here
and now, in this laboratory– the instances experimented upon
These instances are typical = they are representatives of types – of experiment (described in FuGO)– of gene product molecules, molecular
functions, cellular components, biological processes (described in GO)
![Page 186: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/186.jpg)
Experimental records
document a variety of instances (particular real-world examples or cases), ranging from instances of gene products (including individual molecules) to instances of biochemical processes, molecular functions, and cellular locations
![Page 187: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/187.jpg)
Experimental records
provide evidence that gene products of given types have molecular functions of given types by documenting occurrences in the real world that involve corresponding instances of functioning.
They document the existence of real-world molecules that have the potential to execute (carry out, realize, perform) the types of molecular functions that are involved in these occurrences.
![Page 188: Ontology and the Future of Biomedical Research Barry Smith](https://reader038.vdocuments.mx/reader038/viewer/2022110207/56649d395503460f94a13e0b/html5/thumbnails/188.jpg)
Motivation: To capture realityInferences and decisions we make are
based upon what we know of reality.An ontology is a computable
representation of biological reality, which is designed to enable a computer to reason over the data we collect about this reality in (some of) the ways that we do.