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The Canonical Life
Barry Smith
http://ontology.buffalo.edu/smith
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Ontology (Phil.)
= the science of the types of objects, qualities, proesses, events, funktions, environments, relations ... in all spheres of reality
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Google hits (in millions) 12.10.06
ontology 24.0
ontology + philosophy 4.6
ontology + information science 7.4
ontology + database 11.1
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ontology (computer science)
(roughly) the construction of standardized classification systems designed to make databases compatible with each other
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National Center for Biomedical Ontology$18.8 mill. NIH Roadmap Center
• Stanford Medical Informatics• University of San Francisco Medical Center• Berkeley Drosophila Genome Project• Cambridge University Department of Genetics• The Mayo Clinic• University at Buffalo Department of Philosophy
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From chromosome
to disease
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genomicstranscriptomicsproteomicsreactomics metabonomics phenomicsbehavioromicsconnectomicstoxicopharmacogenomicsbibliomics
… legacy of Human Genome Project
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we need to know where in the body
we need to know what kind of
disease process
= we need ontologies
we need semantic annotation of data
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how create broad-coverage semantic annotation systems for biomedicine?
covering: in vitro biological phenomenamodel organismshumans
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OBO Foundry Project
ontology developers in the life sciences have agreed in advance to accept a growing set of best practices in ontology development to ensure interoperability and additivity of annotationshttp://obofoundry.org
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Ontology Scope URL Custodians
Cell Ontology (CL)
cell types from prokaryotes to mammals
obo.sourceforge.net/cgi-
bin/detail.cgi?cell
Jonathan Bard, Michael Ashburner, Oliver Hofman
Chemical Entities of Bio-
logical Interest (ChEBI)
molecular entities ebi.ac.uk/chebiPaula Dematos,Rafael Alcantara
Common Anatomy Refer-
ence Ontology (CARO)
anatomical structures in human and model
organisms(under development)
Melissa Haendel, Terry Hayamizu, Cornelius
Rosse, David Sutherland,
Foundational Model of Anatomy (FMA)
structure of the human body
fma.biostr.washington.
edu
JLV Mejino Jr.,Cornelius Rosse
Functional Genomics Investigation
Ontology (FuGO)
design, protocol, data instrumentation, and
analysisfugo.sf.net FuGO Working Group
Gene Ontology (GO)
cellular components, molecular functions, biological processes
www.geneontology.org
Gene Ontology Consortium
Phenotypic Quality Ontology
(PaTO)
qualities of anatomical structures
obo.sourceforge.net/cgi
-bin/ detail.cgi?attribute_and_value
Michael Ashburner, Suzanna
Lewis, Georgios Gkoutos
Protein Ontology (PrO)
protein types and modifications
(under development)Protein Ontology
Consortium
Relation Ontology (RO)
relationsobo.sf.net/
relationshipBarry Smith, Chris
Mungall
RNA Ontology(RnaO)
three-dimensional RNA structures
(under development) RNA Ontology Consortium
Sequence Ontology(SO)
properties and features of nucleic sequences
song.sf.net Karen Eilbeck
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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?
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where in the cell ?
what kind of biological process ?
what kind of molecular function?
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GO’s three ontologies
molecular functions
cellular components
biological processes
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Three granularities:
Cellular (for components)
Molecular (for functions)
Organ + organism (for processes)
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The Granularity Gulf
most existing data-sources are of fixed, single granularity
many (all?) clinical phenomena cross granularities
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GO’s three ontologies
molecular function
cellular component
biological process
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GO’s three ontologies
molecular function
cellular component
organism-level
biological process
cellularprocess
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molecular function
molecule
cellularprocess
cellular component
organism-level
biological process
organism
Normalization of Granular Levels
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need to separate function from activity
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moleculecellular
component
molecular function
cellularfunction
organism-level
biological function
organism
molecular process
cellularprocess
organism-level
biological process
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types of process
stochastic processes (Brownian motion of blood cells)
accidents (heart penetrated by bullet)
functionings (heart pumping) (elite processes)
side-effects (heart beating)
malfunctionings ...
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moleculecellular
component
molecular function
cellularfunction
organism-level
biological function
organism
molecular process
cellularprocess
organism-level
biological process
functioning functioning functioning
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molecular function
cellularfunction
organism-level
biological function
molecular process
cellularprocess
organism-level
process
functioningsfunctionings functionings
The new age of teleology
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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
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Problem of aging and death
are their parts of the organism involved in bringing about aging processes?
is this their function?
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Problem of reproductive organs
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
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Problem of reproductive organs
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 a group’s survival
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Problem of reproductive organs
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 genes’ survival
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Functions are organized in a modular hierarchy
The function of each functional part is: to contribute to the functioning of the whole
we need to understand ‘function’ in relation to the actual environing whole of the part in question
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What do the kidneys do?
The function of the kidney is to purify blood
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How does a kidney work?The nephron is the cardinal functional unit of the kidney
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Nephron Functions10 functional segments15 different cell types
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Challenge
Can we provide an account of the functions of sexual organs within this framework
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
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Function is what gives rise to normal activity
But: that sperm function (to penetrate the ovum) is rare
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Functions
This is a screwdriver
This is a good screwdriver
This is a broken screwdriver
This is a heart
This is a healthy heart
This is an unhealthy heart
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Functions and Prototypes
In its functioning, a heart creates a four-dimensional process shape. Good hearts create other process shapes than sick hearts do.
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Prototypes
functioning
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poor functioning
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malfunctioning
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not functioning at all
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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)
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What is health
Boorse: the state of an organism is theoretically healthy, i.e., free from disease, in so far as its mode of functioning conforms to the natural design of that kind of organism
= all its functional parts function in such a way as to promote survival and reproduction
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The Gene Ontology
is a canonical ontology – it represents only what is normal in the realm of (molecular) functioning
= what pertains to normal (‘wild type’) organisms (in all species)
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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.
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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.
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molecule cellular component
molecular function
cellularfunction
organism-level
biological function
organism
molecular process
cellularprocess
organism-level
process
functioningsfunctionings functionings
everything here is typical
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Ontology Scope URL Custodians
Cell Ontology (CL)
cell types from prokaryotes to mammals
obo.sourceforge.net/cgi-
bin/detail.cgi?cell
Jonathan Bard, Michael Ashburner, Oliver Hofman
Chemical Entities of Bio-
logical Interest (ChEBI)
molecular entities ebi.ac.uk/chebiPaula Dematos,Rafael Alcantara
Common Anatomy Refer-
ence Ontology (CARO)
anatomical structures in human and model
organisms(under development)
Melissa Haendel, Terry Hayamizu, Cornelius
Rosse, David Sutherland,
Foundational Model of Anatomy (FMA)
structure of the human body
fma.biostr.washington.
edu
JLV Mejino Jr.,Cornelius Rosse
Functional Genomics Investigation
Ontology (FuGO)
design, protocol, data instrumentation, and
analysisfugo.sf.net FuGO Working Group
Gene Ontology (GO)
cellular components, molecular functions, biological processes
www.geneontology.org
Gene Ontology Consortium
Phenotypic Quality Ontology
(PaTO)
qualities of anatomical structures
obo.sourceforge.net/cgi
-bin/ detail.cgi?attribute_and_value
Michael Ashburner, Suzanna
Lewis, Georgios Gkoutos
Protein Ontology (PrO)
protein types and modifications
(under development)Protein Ontology
Consortium
Relation Ontology (RO)
relationsobo.sf.net/
relationshipBarry Smith, Chris
Mungall
RNA Ontology(RnaO)
three-dimensional RNA structures
(under development) RNA Ontology Consortium
Sequence Ontology(SO)
properties and features of nucleic sequences
song.sf.net Karen Eilbeck
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The Foundational Model of Anatomy is a canonical representation
= a 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.
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FMA
recognizes also variant anatomical structures (e.g. coronary arteries or bronchopulmonary segments which deviate from the canonical anatomical pattern of organization)
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A solution
Canonical anatomy = anatomy of the canonical human being in the canonical anatomical position (no amputation stumps, no effects of steroids, …)
For each type of organism there is a canonical Bauplan, but there is also a canonical life plan (canonical life Gestalt)
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Model organisms
you can buy a mouse with the prototypical mouse Bauplan according to a precise genetical specification
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Canonical lifeplan = the physiological counterpart of
canonical anatomy
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the canonical life (plan)
birth infancy teenagerdom early adulthood maturity late adulthood death
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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
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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
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This canonical life plan might include
canonical embryological development
canonical growth
canonical reproduction
canonical aging
canonical death
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For all animals the canonical life Gestalt includes:
canonical embryological development
canonical growth
canonical reproduction
canonical aging
canonical death
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For non-human organisms the canonical life Gestalt is primarily
canonical physiology
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• spontaneity
• society
• culture
• technology
For a human being the canonical life Gestalt includes:
birth infancy teenagerdom early adulthood maturity late adulthood death
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canonical life Gestalten
+ variant life Gestalten (vegetarians, lesbians)
+ pathological life Gestalten (serial murderers)
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What would the life of a wild type human being involve?
Reproduction ...
Aging ...
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Just as there are 2 x n canonical Baupläne for human beings (male
and female at n successive stages)
so there may be different canonical life plans for different types of human beings
if so, what are the different types?
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Is talk of ‘life plan’ descriptive or prescriptive
If prescriptive we can use it as a benchmark e.g. to measure the success of different policies
Use it as a measure of flourishing
Relevance to debates about endangered species
Relevance to debates about ‘what is a life worth living?’
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What is life?
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What is a canonical environment?
What is a canonical family?
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What does every human canonical life involve
9 months of development
later acquisition of consciousness, language ...
cycles of waking, sleeping
death
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Different perspectives on the canonical life
Aristotle: the golden meanCatholic: no contraception, no sinEvolutionary psychology: life in the African
savannahRoger Barker: behavior settingsClinical medicine: goal to bring patient back in the
direction of a canonical lifeCryonics view: ‘life’ is defined entirely
conventionallyTranshumanism
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