Http://org.buffalo.edu 1 The Canonical Life Barry Smith .

http://org.buffalo.edu

The Canonical Life

Barry Smith

http://ontology.buffalo.edu/smith

Ontology (Phil.)

= the science of the types of objects, qualities, proesses, events, funktions, environments, relations ... in all spheres of reality

Google hits (in millions) 12.10.06

ontology 24.0

ontology + philosophy 4.6

ontology + information science 7.4

ontology + database 11.1

ontology (computer science)

(roughly) the construction of standardized classification systems designed to make databases compatible with each other

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

From chromosome

to disease

genomicstranscriptomicsproteomicsreactomics metabonomics phenomicsbehavioromicsconnectomicstoxicopharmacogenomicsbibliomics

… legacy of Human Genome Project

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

how create broad-coverage semantic annotation systems for biomedicine?

covering: in vitro biological phenomenamodel organismshumans

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

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.

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

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?

where in the cell ?

what kind of biological process ?

what kind of molecular function?

GO’s three ontologies

molecular functions

cellular components

biological processes

Three granularities:

Cellular (for components)

Molecular (for functions)

Organ + organism (for processes)

The Granularity Gulf

most existing data-sources are of fixed, single granularity

many (all?) clinical phenomena cross granularities

molecular function

cellular component

biological process

molecular function

cellular component

organism-level

biological process

cellularprocess

molecular function

molecule

cellularprocess

cellular component

organism-level

biological process

organism

Normalization of Granular Levels

need to separate function from activity

moleculecellular

component

molecular function

cellularfunction

organism-level

biological function

organism

molecular process

cellularprocess

organism-level

biological process

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 ...

moleculecellular

component

molecular function

cellularfunction

organism-level

biological function

organism

molecular process

cellularprocess

organism-level

biological process

functioning functioning functioning

molecular function

cellularfunction

organism-level

biological function

molecular process

cellularprocess

organism-level

process

functioningsfunctionings functionings

The new age of teleology

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

Problem of aging and death

are their parts of the organism involved in bringing about aging processes?

is this their function?

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

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

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

What do the kidneys do?

The function of the kidney is to purify blood

How does a kidney work?The nephron is the cardinal functional unit of the kidney

Nephron Functions10 functional segments15 different cell types

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

Function is what gives rise to normal activity

But: that sperm function (to penetrate the ovum) is rare

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

Functions and Prototypes

In its functioning, a heart creates a four-dimensional process shape. Good hearts create other process shapes than sick hearts do.

Prototypes

functioning

poor functioning

malfunctioning

not functioning at all

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)

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

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)

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.

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.

molecule cellular component

molecular function

cellularfunction

organism-level

biological function

organism

molecular process

cellularprocess

organism-level

process

functioningsfunctionings functionings

everything here is typical

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.

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

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.

recognizes also variant anatomical structures (e.g. coronary arteries or bronchopulmonary segments which deviate from the canonical anatomical pattern of organization)

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)

Model organisms

you can buy a mouse with the prototypical mouse Bauplan according to a precise genetical specification

Canonical lifeplan = the physiological counterpart of

canonical anatomy

the canonical life (plan)

birth infancy teenagerdom early adulthood maturity late adulthood death

What does “function” mean?

the function is this disposition

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

This canonical life plan might include

canonical embryological development

canonical growth

canonical reproduction

canonical aging

canonical death

For all animals the canonical life Gestalt includes:

canonical embryological development

canonical growth

canonical reproduction

canonical aging

canonical death

For non-human organisms the canonical life Gestalt is primarily

canonical physiology

• spontaneity

• society

• culture

• technology

For a human being the canonical life Gestalt includes:

birth infancy teenagerdom early adulthood maturity late adulthood death

canonical life Gestalten

+ variant life Gestalten (vegetarians, lesbians)

+ pathological life Gestalten (serial murderers)

What would the life of a wild type human being involve?

Reproduction ...

Aging ...

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?

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?’

What is life?

What is a canonical environment?

What is a canonical family?

What does every human canonical life involve

9 months of development

later acquisition of consciousness, language ...

cycles of waking, sleeping

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

Http://org.buffalo.edu 1 The Canonical Life Barry Smith .

Documents

Transcript of Http://org.buffalo.edu 1 The Canonical Life Barry Smith .

2D Canonical Forms, Isometric PEPS CanF.1 1. Canonical ...

Contentskollar/book/chap2.pdf · Contents Chapter 2. Canonical Models 3 1. Canonical singularities and canonical models 3 2. Examples of log canonical singularities 22 3. Surface

Canonical Form

Http://ontologist.com 1 Approaches to Ontology Creation Barry Smith .

Canonical Pb

Http://ontologist.com1 HL7 RIM Exegesis and Critique Regenstrief Institute, November 8, 2005 Barry Smith Director National Center for Ontological Research.

Feature-Preserved 3D Canonical Form · Sect. 2. Perhaps, the utilization of canonical forms (unless otherwise speciﬁed, canonical form mentioned in this pa-per means the canonical

CCA: An R Package to Extend Canonical Correlation Analysis · Keywords: canonical correlations, regularization, cross-validation. 1. Introduction Canonical correlation analysis (CCA)

Http://ifomis.org 1 Ontologie des Dokuments Barry Smith Institute for Formal Ontology and Medical Information Science Saarbrücken Department of Philosophy.

Canonical Shaders for Optimal Performance Canonical Shaders for

Finite Density with Canonical Ensemble and the Sign Problem Finite Density Algorithm with Canonical Ensemble Approach Finite Density Algorithm with Canonical.

Http://ifomis.org 1 Sprechakte und Dokumentenakte Barry Smith Institute for Formal Ontology and Medical Information Science Saarbrücken Department of Philosophy.

Rational Canonical Formbuzzard.ups.edu/...spring...canonical-form-present.pdfIntroductionk[x]-modulesMatrix Representation of Cyclic SubmodulesThe Decomposition TheoremRational Canonical

Canonical Tradition

Http://ncor.us 1 Why computer science needs philosophy Barry Smith National Center for Ontological Research.

Canonical Correlation. What is Canonical Correlation? Canonical correlation seeks the weighted linear composite for each variate (sets of D.V.s or I.V.s)

About Canonical

Canonical Quantization

Canonical Ideal

Http://ontologist.com 1 The Ontology of Documents Barry Smith.