1 Forms of Life Barry Smith . 2

Forms of Life

Barry Smith

http://ifomis.org

Protein

Organelle

Tissue

Organism

10-5 m

10-1 m

Scales of anatomy

10-9 m

New Golden Age of Classification

30,000 genes in human200,000 proteins100s of cell types100,000s of disease types 1,000,000s of biochemical pathways

(including disease pathways)

… legacy of Human Genome Project

FUNCTIONAL GENOMICS

proteomics,

reactomics,

metabonomics,

phenomics,

behaviouromics,

toxicopharmacogenomics

The problem is:each (chemical, clinical, pathological, immunological, toxicological, pharmacological, anatomical …) information system uses its own classification system

How can we overcome the incompatibilities which become apparent when data from distinct sources is combined?

Answer:

“Ontology”

Google hits (as of yesterday)

ontology + philosophy 143K

ontology + engineering 145K

ontology + information systems 217K

ontology + software 252K

ontology + database 279K

IFOMIS

Institute for Formal Ontology

and Medical Information Science

The problem of the unity of science

The logical positivist solution to this problem addressed a world in which sciences are associated with

printed texts

What happens when sciences are associated with databases ?

A Linnaean Species Hierarchy

Medical Diagnostic Hierarchy

a hierarchy in the realm of diseases

Combining hierarchies

Organisms Diseases

via Dependence Relations

Organisms Diseases

A Window on Reality

Organisms Diseases

A Window on Reality

The UMLS

Unified Medical Language System

contains information about over 1 million biomedical concepts and 2.8 million concept names from more than 100

controlled vocabularies and classifications

UMLS Source Vocabularies

SNOMED – Systematized Nomenclature of Medicine

ICD International Classification of Diseases

MeSH – Medical Subject Headings

GO – Gene Ontology

FMA – Foundational Model of Anatomy

To reap the benefits of standardization

we need to make ONE SYSTEM out of many different terminologies

= UMLS “Semantic Network”nearest thing to an “ontology” of the UMLS

134 Nodes, 54 Relationship-Types between these Nodes, forming a graph with 6000 Edges

21Fragment of the UMLSemantic Network

UMLS Semantic Network

entity event

physical conceptual object entity

organism

conceptual entity

Organism Attribute

Finding

Idea or Concept

Occupation or Discipline

Organization

Group Attribute

Intellectual Product

Language

Idea or ConceptFunctional ConceptQualitative ConceptQuantitative ConceptSpatial Concept

Body Location or RegionBody Space or JunctionGeographic AreaMolecular Sequence

Amino Acid SequenceCarbohydrate SequenceNucleotide Sequence

Trattenbach

is an Idea or Concept

Idea or ConceptFunctional ConceptQualitative ConceptQuantitative ConceptSpatial Concept

Body Location or RegionBody Space or JunctionGeographic AreaMolecular Sequence

Amino Acid SequenceCarbohydrate SequenceNucleotide Sequence

Problem: Confusion of concepts and entities in reality

Blood Pressure Ontology

The hydraulic equation:

BP = CO*PVR

arterial blood pressure (BP) is directly proportional to the product of blood flow (cardiac output, CO) and peripheral vascular resistance (PVR).

UMLS-Semantic Types:

blood pressure is an Organism Function,

cardiac output is a Laboratory or Test Result or Diagnostic Procedure

BP = CO*PVR thus asserts that

blood pressure is proportional either to a laboratory or test result or to a diagnostic procedure

Problem: Confusion of reality with our (ways of gaining) knowledge

about reality

What are the terms of ontologies in the ontological engineering sense

Answer: Concepts

‘Concept’

Semantic Network Definition:

Concept =def. An abstract concept, such as a social, religious, or philosophical concept

UMLS Definition:

Concept =def. A class of synonymous terms

Trattenbach is_a class of synonymous terms

entity

organism

Concept A is_a Concept B

is_a =def.

If one item ‘is_a’ another item then the first item is more specific in meaning than the second item. (Italics added)

fish is_a vertebrate

enzyme is_a biologically active substance

copulation is_a biological process

How can concepts figure as relata of these relations?

part_of = def. Composes, with one or more other physical units, some larger whole

causes =def. Brings about a condition or an effect.

contains =def. Holds or is the receptacle for fluids or other substances. This includes filled with, holds, and is occupied by

embryonic structure part_of human

–embryonic structures appear as parts of entities other than humans

–humans have embryonic structures as parts only in certain phases of their existence

Acquired Abnormality affects Fish

Experimental Model of Disease affects Fungus

Food causes Experimental Model of Disease

Biomedical or Dental Material causes Mental or Behavioral Dysfunction

Manufactured Object causes Disease or Syndrome

Vitamin causes Injury or Poisoning

Tissue location_of Mental or Behavioral Dysfunction

The Concept OrientationWork on biomedical ontologies grew out of work on

medical dictionaries and nomenclaturesHas focused almost exclusively on ‘concepts’ conceived

(sometimes called ‘classes’, sometimes confused with terms/descriptions).

Concept-orientation also common in KR, has led to the entrenchment of an assumption according

to which all that need be said about classes can be said without appeal to time or instances.

This, however, has fostered an impoverished regime of definitions in which the use of identical terms (like ‘part’) in different systems has been allowed to mask underlying incompatibilities.

Belnap

“it’s a good thing logicians were around before computer scientists;

“if computer scientists had got there first, then we wouldn’t have numbers

because arithmetic is undecidable”

INSTANcES ARE SINGLETONS

BelnapHilbert's formalism is Kantianism (Cabalah) reference is one address writing to another addressesmolecules have their parts rigidly10 Billion Pounds for SNOMEDInfluence of GOBad things in GOOntologies in BIO generally (google)Functions, processesPancreas gene storyinhibition/function/regulation/plasticity/redundancy/deathEvolution is opportunistic (= opportunistic infections) = good for bacteria etc.against Millikan -- cell death

life plan = physiology = changes in qualities of partsgrowth - getting biggerdevelopment = new kinds of things getting formedaging = involutiondeath

Aristotle-Linnaeus Theory of Species and Instances

siamese

mammal

organism

substancespecies, genera

animal

instances

Husserl’s Science of Pure Logic

siamese is P

mammal is P

cat is P

S is P

judgmentspecies, genera

animal is P

instances… … … … … …

a stands in R to something

a stands in R to b

siamese is P

mammal is P

cat is P

S is P

judgmentspecies, genera

animal is P

a stands in R to something

a stands in R to b

LAWS OF LOGIC = LAWS OF ESSENCE GOVERNING STRUCTURES/COMBINATIONS OF JUDGMENT

The historical epistemology of the sciences

life-world

physics

medicine

molecular biology

granularity

Different scientific cultures/terminologies

immunology

genetics

cell biology

(Quine)

an ‘ontology’ is a systematic representation of the ontological commitments of a given scientific discipline, culture, commercial enterprise …

children’s ontology

Buddhist ontology

wine ontology

Ontologies as hierarchies of ‘concepts’

“Concepts, also known as classes, are used in a broad sense. They can be abstract or concrete, elementary or composite, real or fictious. In short, a concept can be anything about which something is said, and, therefore, could also be the description of a task, function, action, strategy, reasoning process, etc.”

Confusion of concept / object / description

Semantic Web

Ontology-based unification =

REDUCE EVERYTHING TO SYNTACTIC STRINGS IN SOME ‘Ontology Web Language’

and STIR VIGOROUSLY

The Crisis of Bioinformatic Sciences

An alternative research programme for ontology

based on philosophical principles

Department of Biological Structure (Seattle)

Ontek Corporation (Buffalo)

Laboratory for Applied Ontology (Trento/Rome)

Basic Formal Ontology

(counterpart of pure mathematics)

A Network of Domain Ontologies

Material (Regional) Ontologies

PsychO

GO ARO

PhysiO

Part ThreeARO: The Anatomy Reference Ontology

Anatomy Reference Ontology =

theoretical framework surrounding the Digital Anatomist Foundational Model of Anatomy of Department of Biological Structure, University of Washington, Seattle

Anatomical Entity

Physical Anatomical Entity

Material Physical Anatomical Entity

-is a-

Non-material Physical Anatomical Entity

ConceptualAnatomical Entity

AnatomicalStructure

BodySubstance

BodyPart

HumanBody

OrganSystem

OrganCell

OrganPart

AnatomicalSpace

Anatomical Relationship

CellPart

Biological Macromolecule

Tissue

A Linnaean HierarchyAnatomical Entity

Physical Anatomical Entity

Material Physical Anatomical Entity

-is a-

Non-material Physical Anatomical Entity

ConceptualAnatomical Entity

AnatomicalStructure

BodySubstance

BodyPart

HumanBody

OrganSystem

OrganCell

OrganPart

AnatomicalSpace

Anatomical Relationship

CellPart

Biological Macromolecule

Tissue

at every level of granularity

Anatomy Reference Ontology

“Rather than stating the meanings of terms, definitions should state the essence of anatomical entities in terms of their characteristics ... Paraphrasing Aristotle, the essence of an entity is constituted by … the genus, necessary to assign an entity to a class and … the differentiae, necessary to distinguish the entity from other entities also assigned to the class.”

The Anatomy Reference Ontology

is organized in a graph-theoretical structure involving two sorts of links or edges:

is-a (= is a subtype of )

(auditory ossicle is-a bone)

part-of

(cervical vertebra part-of vertebral column)

Part Four

GO: The Gene Ontology

GO is three ontologies

cellular componentsmolecular functions biological processes

December 16, 2003:1372 component terms7271 function terms8069 process terms

GO product of Open Biological Ontologies consortium

Fungal Ontology

Plant Ontology

Yeast Ontology

Disease Ontology

When a gene is identified

three important 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?

GO’s three ontologies

molecular functions

cellular components

biological processes

The Cellular Component Ontology (counterpart of anatomy)

flagellum

chromosome

membrane

cell wall

nucleus

The Molecular Function Ontology

ice nucleation

protein stabilization

kinase activity

binding

The Molecular Function ontology is (roughly) an ontology of actions on the molecular level of granularity

Biological Process Ontology

Examples:glycolysisdeathadult walking behaviorresponse to blue light

= occurrents on the level of granularity of cells, organs and whole organisms

the universals of GO are species-independent

an ontology of the unchanging universal building blocks of life

(substances and processes)

and of the structures they form

but: GO built by biologists

compare: the Gene Statistic

hemolysis

Definition

The cause of hemolysis …

Molecular Function

Definition:

An activity or task performed by a gene product. It often corresponds to something (such as a catalytic activity) that can be measured in vitro.

Biological Process

Definition:

A biological process is a biological goal that requires more than one function. Mutant phenotypes often reflect disruptions in biological processes.

Each of GO’s ontologies

is organized in a graph-theoretical structure involving two sorts of links or edges:

is-a (= is a subtype of )

(copulation is-a biological process)

part-of

(cell wall part-of cell)

GO has only sentences of the form A is_a B and A part_of B

no way to express ‘not’ and no way to express ‘is localized at’ and no way to express ‘I don’t know’:

Holliday junction helicase complex

unlocalized

GO:0008372 cellular component unknown

cellular component unknown is-a cellular component

Is biological classification Linnaean?

Principle of Single Inheritance

no class in a true (Linnaean) hierarchy should have more than one parent on the immediate higher level

no diamonds:

Problems with multiple inheritance

is-a1 is-a2

‘is-a’ no longer univocal

‘is-a’ is pressed into service to mean a variety of different things

the resulting ambiguities make the rules for correct coding difficult to communicate to human curators

they also serve as obstacles to integration with neighbouring ontologies

‘within’

lytic vacuole within a protein storage vacuole

lytic vacuole within a protein storage vacuole is-a protein storage vacuole

time-out within a baseball game is-a baseball game

embryo within a uterus is-a uterus

‘extrinsic to’

extrinsic to membrane

extrinsic to membrane part-of membrane

GO’s three ontologies are separate

No links or edges defined between them

molecular functions

cellular components

Three granularities:

Molecular (for functions)

Cellular (for components)

Whole organism (for processes)

GO does not include molecules or organisms within any of its three

ontologies

The only continuant entities within the scope of GO are cellular components (including cells themselves)

Are the relations between functions and processes a matter of granularity?

Molecular activities are the building blocks of biological processes ?

But they cannot be represented in GO as parts of biological processes

GO does not recognize parthood relations between entities on its

three distinct levels of granularity

Compare:

this wheel is part of the car

this molecule is part of the car

Part Five

Extending GO to make a full ontology by adding relations of dependence

GO must be linked with other neighboring ontologies

GO has: adult walking behavior but not adult

GO has: eye pigmentation but not eye

GO has: response to blue light but not light (or blue)

94% of words used in GO terms are not GO terms

Principle of Dependence

If an ontology recognizes a dependent entity then it (or a linked ontology) should recognize also the relevant class of bearers

Linking to external ontologies

can also help to link together GO’s own three separate parts

molecular functions

cellular components

dependent

independent

molecular functions

cellular components

organism-level

cellularprocesses

molecular functions

moleculecomplexe

cellularprocesses

cellular components

organism-level

organisms

‘part-of’; ‘is dependent on’

moleculecomplexe

cellular component

molecular function

cellularfunctions

organism-level

biological functions

organisms

molecular processe

cellularprocesses

organism-level

moleculecomplexe

cellular component

molecular function

cellularfunctions

organism-level

biological functions

organisms

molecular processe

cellularprocesses

organism-level

functioningsfunctionings functionings

junk processes

– theory of part and whole– theory of dependence– theory of boundary, continuity and contact– ( Aristotelian) theory of species, instances

and lowest specific differences (first edition of LU)

– theory of continuants and occurrents– theory of functions– theory of granularity

The End

The problem

About 30,000 genes in a human

Probably 100-200,000 proteins

Individual variation in most genes

100s of cell types

100,000s of disease types

Protein

Organelle

Tissue

Organism

Muscle tissueNerve tissueConnective tissueEpithelial tissueBlood

Musculo-skeletal systemCirculatory systemRespiratory systemDigestive systemNervous systemUrinary systemReproductive systemEndocrine systemLymphoidal system

MitochondriaNucleusEndoplasmic reticulumCell membrane

The Challenge

Each (clinical, pathological, genetic, proteomic, pharmacological …) information system uses its own terminology and category systembiomedical research demands the ability to navigate through all such information systems How can we overcome the incompatibilities which become apparent when data from distinct sources is combined?

Answer:

“Ontology”

Three senses of ontology

1. Philosophical sense: an inventory of the types of entities and relations in reality

2. Knowledge engineering sense: an ontology as a consensus representation of the concepts used in a given domain

3. GO/OBO sense: a controlled vocabulary

Ontology as a branch of philosophy

seeks to establish

the basic formal-ontological structures

the kinds and structures of objects, properties, events, processes and relations in each material domain of reality

Formal ontology an analogue of pure mathematics

Can be applied to different domains

Material ontology a kind of generalized chemistry or zoology

(Aristotle’s ontology grew out of biological classification)

Aristotle

world’s first ontologist

World‘s first ontology

(from Porphyry’s Commentary on Aristotle’s Categories)

Linnaean Ontology

Formal Ontology– theory of part and whole– theory of dependence / unity– theory of boundary, continuity and contact– theory of universals and instances – theory of continuants and occurrents (objects

and processes)– theory of functions and functioning– theory of granularity

Formal Ontology

the theory of those ontological structures

(such as part-whole, universal-particular)

which apply to all domains whatsoever

Formal Ontology vs. Formal Logic

Formal ontology deals with the interconnections of things

with objects and properties, parts and wholes, relations and collectives

Formal logic deals with the interconnections of truths

with consistency and validity, or and not

Formal Ontology vs. Formal Logic

Formal ontology deals with formal ontological structures

Formal logic deals with formal logical structures

(Epistemology deals with ways of gaining knowledge)

Formal-Ontological Categoriessubstanceprocessfunctionunitypluralitysitedependent partindependent part

are able to form complex structures in non-arbitrary ways joined by relations such as part, dependence, location.

Example of a Formal-Ontological Structure

Ontological Structure

two-sided mutual dependence

one-sided dependence

Ontological Structure

part-whole

relation

Material (Regional) Ontologies

In formal ontology

as in formal logic, we can grasp the properties of given structures in such a way as to establish in one go the properties of all formally similar structures

Material Ontology of Social Interaction

oblig-ation

promiser

promisee

act of speaking

act of registering

content

A Window on Reality

oblig-ation

promiser

promisee

act of speaking

act of registering

content

Universals

oblig-ation

promiser

promisee

act of speaking

act of registering

content

Instances

oblig-ation

promiser

promisee

act of speaking

act of registering

content

A Window on Reality

Medical Diagnostic Hierarchy

a hierarchy in the realm of diseases

Dependence Relations

Organisms Diseases

A Window on Reality

Organisms Diseases

A Window on Reality

siamese

mammal

organism

substanceuniversals

animal

instances

Many current standard ‘ontologies’ ramshackle because they have no

counterpart of formal ontologyThe Universal Medical Language System (UMLS)

a compendium of source vocabularies including:

HL7 RIM

SNOMED

International Classification of Diseases

MeSH – Medical Subject Headings

Gene Ontology

Problem: The different source vocabularies are incompatible with

each other

Problem: They contain bad coding

which often derives from failure to pay attention to simple logical or ontological principles or from principles of good definitions

Bad Coding

Plant roots is-a Plant

Plant leaves is-a Plant

Pollen is-a Plant

Both testes is a testis

Both uterii is a uterus

Bad definitions

Heptolysis =def the cause of heptolysis

Biological process =def a biological goal that requires more than one function

Standard definition:

A is-a B =def every instance of A is an instance of B

= standard definition of computer science

adult is-a child

animal owned by the Emperor is-a animal

mammal is-a object weighing less than 200 kg

correct reading of is-a

1. A and B are natural kinds,

2. there are times at which instances of A exist,

3. at all such times these instances are necessarily (of their very nature) also instances of B

1. eukaryotic cell is-a cell

2. mammal is-a animal

3. death is-a biological process

Ontologies

Here A and B are universals

(= natural kinds, types …, roughly analogous to biological species)

Universals have instances (you and me, your headache, my coughing)

Instances are elite individuals

they are those which instantiate universals (entering into biological laws)

Linnaean Ontology

Confusion of Ontology and Epistemology

Physical Object

Substance

Food Chemical Body Substance

Confusion of Ontology and Epistemology

Chemical

Chemical Chemical

Viewed Viewed

Structurally Functionally

Chemical

Chemical ChemicalViewed Viewed

Inorganic Organic Enzyme Biomedical or Chemical Chemical Dental Material

Chemical

Chemical Chemical

Viewed Viewed

Inorganic Organic Biomedical or

Chemical Chemical Dental Material

Enzyme

Is biological classification Linnaean?

Principle of Single Inheritance

(rule of thumb) no class in a classificatory hierarchy should have more than one parent

The Problem of Multiple Inheritance

Buicks blue cars

blue Buicks

Principle of Taxonomic Levels

the terms in a classificatory hierarchy should be divided into predetermined levels (analogous to the levels of kingdom, phylum, class, order, etc., in traditional biology).

‘depth’ in GO’s hierarchies not determinate because of multiple inheritance

Principle of Exhaustiveness

the classes on any given level should exhaust the domain of the classificatory hierarchy.

Single Inheritance + Exhaustiveness = JEPD

Exhaustiveness often difficult to satisfy in the realm of biological phenomena; but its acceptance as an ideal is presupposed as a goal by every scientist.

Single inheritance accepted in all traditional (species-genus) classifications

is-a1 is-a2

‘sibling’ is no longer determinate

is-a1 is-a2

‘is_a’ is no longer univocal

when ‘is-a’ is pressed into service to mean a variety of different things

the resulting ambiguities make the rules for correct coding difficult to communicate to human curators

they also serve as obstacles to integration with neighboring ontologies

How are universals and instances related together?

Entities

universals (classes, types, taxa, …)

particulars (individuals, tokens, instances …)

Axiom: Nothing is both a universal and a particular

Two Kinds of Elite Entities

classes, within the realm of universals

instances within the realm of particulars

Entities

classes

Entities

classes*

*natural, biological

Entities

classes of objects, substances

need modified axioms for classes of functions, processes, pathways, reactions, etc.

Entities

classes

instances

Classes are natural kinds

Instances are natural exemplars of natural kinds

(problem of non-standard instances)

Not all individuals are instances of classes

Entities

classes

instancesinstances

penumbra of borderline cases

Entities

classes

instances

junkjunk

example of junk: beachball-desk

Primitive relations: inst and part

inst(Jane, human being)

part(Jane’s heart, Jane’s body)

A class is anything that is instantiated

An instance as anything (any individual) that instantiates some class

Entities

Jane’s heart part Jane

part as a relation between individuals

subject to the usual axioms of mereology

Two primitive relations: inst and part

inst(Jane, human being)

part(Jane’s heart, Jane’s body)

A universal is anything that is instantiated

An instance is anything (any individual) that instantiates some class

Two primitive relations: inst and part

Axioms governing inst : (1) it holds in every case between an instance and a

class, in that order; (2) that nothing can be both an instance and a class.

Axioms governing part (= ‘proper part’) (1) it is irreflexive (2) it is asymmetric (3) it is transitive (4) it holds only between individuals (usual mereological axioms)

Part_for and Has_Part

A part_for B =def given any x, if inst(x, A) then there is some y such that inst(y, B) and part(x, y)

B has_part A =def given any y, if inst(y, B) then there is some x such that inst(x, A) and part(x, y)

human testis part_for human being,

But not: human being has_part human testis. human being has_part heart,

But not: heart part_for human being.

The usual part_of relation as a relation between universals

A part_of B =def A part_for B & B has_part A

As exist only as parts of Bs and Bs are structurally organized in such a way that As must appear in them as parts.

Analogous problems for nearly all foundational relations of ontologies and semantic networks:

A causes B

A is associated with B

A is located in B

Reference to instances is necessary to clear up these problems

if they can be cleared up at all …

Mental Process precedes Molecular Function Mental Process precedes Genetic FunctionExperimental Model of Disease precedes Cell or

Molecular DysfunctionAcquired Abnormality affects BirdExperimental Model of Disease affects FungusPhysiologic Function affects ReptileAntibiotic causes Experimental Model of DiseaseBiomedical or Dental Material causes Mental or

Behavioral DysfunctionManufactured Object causes Disease or SyndromeVitamin causes Injury or PoisoningFungus location_of VitaminOrganization location_of Diagnostic Procedure

What are universals?

invariants in reality

satisfying biological laws(there are truths about universals in

biological textbooks)

Universals are Not Sums

Universals are distinguished by granularity: they divide up the corresponding domain into whole units or members, whose interior parts and structure are traced over. The universal human being is instantiated only by human beings as single, whole units.

A mereological sum is not granular in this sense(molecules are parts of the mereological sum of human beings)

Universals are Not SetsBoth universals and sets are marked by

granularity – but universals are timelessBoth a universal and a set is laid across reality like a

grid consisting (1) of a number of slots or pigeonholes each (2) occupied by some member.

But a set is determined by its members. This means that it is (1) associated with a specific number of slots, each of which (2) must be occupied by some specific member.

A universal survives the turnover in its instances: it is specified neither (1) what the number of associated slots should be nor (2) what individuals should occupy these slots. Both may vary with time.

A universal is not determined by its instances as a state is not determined by its citizens

A universal may vary with time as an organism may vary with time (by gaining and losing molecules)

Universals are Not Sets

A set is an abstract structure, existing outside time and space. The set of Romans timelessly has Julius Caesar as a member.Universals exist in time.

Two Questions

1. What does “Functional” mean in expressions like “Functional Genomics” ?

2. How can we use the answer to this question to help us understand notions fundamental to medicine such as “health” and “disease” ?

Towards an Tri-Categorial Ontology

of Structures, Functions and Processes

Definition of Function in UMLS Semantic Network

Functional Concept =df A concept which is of interest because it pertains to the carrying out of a process or activity.

Function Functional Concept

Function Realization of a Function

What do the kidneys do?

Your entire blood volume flows through your kidneys every few minutes, leaving behind excess water, solutes and waste materials

The KidneyFrom Andrew Lonie, University of Melbourne

How does a kidney work?

Essentially a massively parallel filter composed of 105 to 106 nephrons

The nephron is the functional unit of the kidney

Each nephron is a very convoluted, long, thin tube lined with biochemical pumps

Nephron Functions

10 functional segments15 different cell types

Qualitativefunctionalontology

Normal PhysiologyDisease StatesGenetics/MutationsSpecies Differences

Structural ontology

KidneyRenal architecture

Tubule section/Glomerulus

Cell= ANATOMY AT

DIFFERENT LEVELS OF GRANULARITY

Structural and functional representation

process ontology

(molecular, cellular, organ-level …)

entity event

organism

Tri-Categorial Ontology present also in GO: The Gene Ontology

3 ‘ontologies’ (large telephone directories) of standardized designations for gene functions and products

RUMLS Semantic Network

entity event

structures functions processes

GO’s three disjoint term hierarchies

the cellular component (structure) ontology,

e.g. flagellum, chromosome, cell

the biological process ontology,

e.g. glycolysis, death

the molecular function ontology,

e.g. ice nucleation, binding, protein stabilization

RUMLS Semantic Network

entity event

structures functions processes

Functional Genomics

What does “Functional“ mean?

The Problem

The tumor developed in John’s lung over 25 years

The Problem

____ developed in _____ over 25 years

process

The Problem

The tumor developed in the lung over 25 years

substances

things

objects

continuants

The Problem

The tumor developed in John’s lung over 25 years

PARTHOOD NOT DETERMINATE

The Problem

The tumor developed in the lung over 25 years

substances

GLUING THESE TOGETHER YIELDS ONTOLOGICAL MONSTERS

processes

Substances and processes exist in time in different ways

substance

process

SNAP vs SPAN

Endurants vs perdurants

Continuants vs occurrents

In preparing an inventory of reality

we keep track of these two different kinds of entities in two different ways

Fourdimensionalism

– only processes exist

– time is just another dimension, analogous to the three spatial dimensions

– substances are analyzed away as worms/fibers within the four-dimensional plenum

There are no substances

Bill Clinton does not exist

Rather: there exists within the four-dimensional plenum a continuous succession of processes which are similar in a Billclintonizing way

Fourdimensionalism (the SPAN perspective) is right in

everything it says

But incomplete

Need for Two Orthogonal, Complementary Perspectives

SNAP and SPAN

Snapshot Video ontology ontology

substance

process

SNAP and SPAN

stocks and flows

commodities and services

product and process

anatomy and physiology

SNAP and SPAN

SNAP entities

- have continuous existence in time

- preserve their identity through change

- exist in toto if they exist at all

SPAN entities

- have temporal parts

- unfold themselves phase by phase

- exist only in their phases/stages

You are a substance

Your life is a process

You are 3-dimensional

Your life is 4-dimensional

Many SNAP Ontologies

here time exists outside the ontology, as an index or time-stamp

each SNAPi section through reality

includes everything which exists (present tense)

mereology works without restriction (parthood is everywhere determinate) in

every SNAPi ontology

Three kinds of SNAP entities

1. SNAP Independent Entities (you and me)

2. SNAP Dependent Entities

3. Spatial regions

SNAP dependent entities

States, powers, qualities, functions, dispositions, plans, shapes, liabilities,

propensities…

SNAP dependent entities:

one-place:

your temperature, color, heightmy knowledge of French

the whiteness of this cheese the warmth of this stone

the fragility of this glass

relational SNAP dependent entities

John Mary

stand in relations of one-sided dependence to a plurality of substances simultaneously

one-sided dependence

A Window on Reality

oblig-ation

promiser

promisee

act of speaking

act of registering

content

Spatial regions + sites (contexts, niches, environments)

Organism species evolve into environments

Domesticated spatial regions: rooms, nostrils, your alimentary tract

Fiat spatial regions: JFK designated airspace

SNAP: Entities existing in toto at a time

http://ontology.buffalo.edu/bfo

The SPAN Ontology

t i m e

here time exists as part of the domain of the ontology

The SPAN ontology

mereology works without restriction everywhere here

t i m e

clinical trial

mereology works without restriction everywhere here

t i m e

course of a disease

Processes, too, are dependent on substances

One-place vs. relational processes

One-place processes:

your getting warmer

your getting hungrier

Relational processes

kissings, thumpings, conversations,

dancings, promisings, infectings, bindings

join their carriers together into collectives of greater or lesser duration

SPAN: Entities extended in time

SPANEntity extended in time

Portion of Spacetime

Fiat part of process *First phase of a clinical trial

Spacetime worm of 3 + Tdimensions

occupied by life of organism

Temporal interval *projection of organism’s life

onto temporal dimension

Aggregate of processes *Clinical trial

Process[±Relational]

Circulation of blood,secretion of hormones,course of disease, life

Processual Entity[Exists in space and time, unfolds

in time phase by phase]

Temporal boundary ofprocess *

onset of disease, death

http://ontology.buffalo.edu/bfo

Two kinds of SPAN entities

1. Processes (including events: process-boundaries, settings)

2. Spatio-temporal regions

How do you know whether an entity is SNAP or SPAN?

problem cases

forest fire

hurricane Maria

traffic jam

ocean wave

disease

anthrax epidemic

forest fire:

a process

a pack of monkeys jumping from tree to tree and eating up the trees as they go

the Olympic flame:

a process or a thing?

(anthrax spores are little monkeys)

A disease

The course/history of a disease

The Epidemic (SNAP)

The Spread of an Epidemic (SPAN)

Material examples:

performance of a symphonyprojection of a filmexpression of an emotionutterance of a sentenceapplication of a therapyincrease of temperature

The Tri-Categorial Ontology

SNAP SPAN

structures functions processes= independent = dependent continants continuants

The Tri-Categorial Ontology

continuants occurrents

A Window on Reality

continuants occurrents

Entities in all three categories exist both as universals and as instances (as tokens and as types)

The function of your heart is: to pump bloodThe function of my heart is: to pump blood

Functions are continuants

The function of your heart begins to exist with the beginning to exist of your heart, and continues to exist, self-identically, until (roughly) your heart ceases to be able to respond if stimulated by your sympathetic and parasympathetic nervous systems

Functions have bearers

The bearer of the function of your heart is: your heart.

Functions are dependent continuants.

The bearers of functions are independent continuants (hearts, screwdrivers …)

Functions are realized

in special sorts of processes called functionings

The processes taking place in or involving entities which are bearers of functions can be divided into two types: those which are realizations of their functions (also called functionings) and processes of other types (junk processes)

Functions can exist even when they are not being realized

Processes (realizations) are causal-energetic

Functions are historical (they exist in time)

but they are also quasi-Platonic

Compare the relation between temperature,

which is quasi-Platonic

and Brownian motion,

which is causal-energetic

Your temperature at t vs. the value of your temperature at t

Your temperature is quasi-Platonic

Your temperature as a determinable is identical from one moment of your existence to the next

This determinable takes on different values at different times

Biological functions are always constituent functions

If X has a biological function then there is some Y of which X is a part and X’s functioning is in the service of / for the benefit of Y

Functions are beneficial

If an organism has a constituent part X, and if X is the bearer of a function Z, then those processes which are the realizations of the function Z are (in normal circumstances) beneficial to the organism

( such as to sustain the organism in existence)

Functional Genomics

= study of what the genes contribute to the organism in the way of survival(Bad genes do not have functions)

Every oncogene is a proto-oncogene

There is functioning, poor functioning, malfunctioning

There is not having a function at all (and this can be either neutral in the stakes of beneficiality or also positively malignant)

Does this sense of ‘function’ correspond to the way biologists talk?

Clinical vs. biological sense of ‘function’

Biologists sometimes talk about biological structures ‘gaining function’ (= being switched on) even where their functioning is not beneficial

Are all functions associated with malfunctionings?

Health – Disease – Illness

Diseased organ = organ predisposed to malfunction

Its functioning is defective

Part Four: Definitions of Health

World Health Organization:

Health is the state of psychological and physical well-being of humans

Biostatistical TheoryChristopher Boorse

Health is conformity to normal species design (as statistically determined).

Abnormally healthy people are therefore in fact sick (?)

The Vital Goal Theory Lennart Nordenfelt

Health is the bodily and mental state of a person which is such that he or she has an ability to realize vital goals, given standard or otherwise accepted circumstances.

Disease is a state or process of a person’s body or mind that tends to cause ill health in the bearer.

The Ordinary Action TheoryK.W.M. Fulford

Health is being able to do what one ordinarily does in the absence of obstruction or opposition.

Illness is failing to do what one ordinarily does in the absence of obstruction or opposition.

The Abnormality TheoryLawrie Reznek

Disease is a state of a person which issues in abnormal behavior; something is an abnormal bodily or mental process if it does standard members of the human species some harm in standard circumstances;something does a person harm if it makes the person less able to live a good or worthwhile life.

Problems with standard definitions

1. Circularity

2. Make health a social construction

3. Make health a Cambridge property

4. Confuse state and process, disposition and realization, potentiality and actuality

5. Do not apply to organisms other than humans

Circularity

Health is ... well-being

Health is ... being able to live a good or worthwhile life

Disease is a state … that tends to cause ill health in the bearer

Health a social construction

Health is …the ability to realize vital goals, given standard or otherwise accepted circumstances

Illness = what the insurance company will pay to treat

Health a Cambridge Property

Health is conformity to normal species design (as statistically determined).

If everyone in society becomes sicker and you remain the same, then you are the person who becomes unhealthy

Ontology of Disease

Diseases are, like functions, dependent continuants

They are states or conditions which endure for a certain time and have a course or history, which is an occurrent

Disease tokens, like roles and functions, do not change through their existence over time

Diseases are both historical and quasi-Platonic

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 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 simultaneously transferring hydraulic pressure to the blood stored within its chambers

For each function

there is an associated family of (four-dimensional) process shapes, organized around a core of prototypical process shapes representing good functioning

The prototypes play a role analogous to the standard meter rule in the organization of those one-dimensional shapes we call lengths

Outside the core

are process shapes which are not instances of functioning at all

Normal functioning

= functioning (realizing a four-dimensional shape) at or close to the prototype

Prototypes

good functioning

Prototypes

reasonable functioning

Poor functioning

poor functioning

Malfunctioning

malfunctioning

Death?

not functioning at all

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 environments

assistance from other organisms

Relevance of Millikan

Prototypical functioning = exercising what Millikan calls ‘proper function’

(defined historically)X is the proper function of Y means: 1) Y

performs X and 2) Y exists because its predecessors’ performing the function X is responsible for my existing

It is not the function of the nose to hold up spectacles because this was not selected for

Millikan = backward looking, focused on whole species

This account = forward looking, focused on single organism

X has a function = (1) X’s functioning is beneficial to the organism of which X is a part

Boorse’s Internal Impairment Theory

Disease is an internal state which is an impairment or limitation of normal functional ability.

Disease

Disease = remoteness from prototypical functioning

disease

Disease = remoteness from prototypical functioning

disease

1 2 3 1 = not functioning at all

2 = malfunctioning

3 = functioning poorly

Not functioning at all

= death modulo:

criticality of the system involved

Biological entities have biological functions only as parts of organisms

An organic entity functions in the service of the organism of which it is a part

There are immediate parts of the organism – the bodily systems – which function directly in the service of the organism.

And there are mediate (= smaller) parts of the organism – cells, tissues, organs … -- which function in the service of larger parts

Immediate parts of the organism are more critical

Bodily Systems

respiratorydigestive skeletal circulatorymusculatory immune

ENDOCRINE

SYSTEM

What do the kidneys do?KIDNEY

How does a kidney work?NEPHRON

Nephron FunctionsFUNCTIONAL SEGMENTS

Protein

Organelle

Tissue

Organism

Coda on ‘Normal’

Normal functioning of the pancreas

Normal functioning of the sexual organs

On the several senses of ‘normal’ in biology

Problem: The Sexual Organs do not have Biological Functions

A constituent part of an organism has a function = its functioning is beneficial to the survival of the host organism

– this does not hold for the reproductive system and its parts

Hence the sexual organs do not have functions

Alternatively they have functions in relation to some larger whole (the family, the dynasty …)

Compare the role of worker bees in bee colonies …

The End

1 Forms of Life Barry Smith . 2

Documents

Ifomis.org International Standard Bad Philosophy Barry Smith

Species and Classification in Biology Barry Smith

VR. Formal Principles for Biomedical Ontologies Barry Smith

How to Organize the World of Ontologies Barry Smith ontology.buffalo/smith

The Environment Ontology Barry Smith 1

Healthcare Information Management Barry Smith 1

Barry Smith, University at Buffalo, NY , USA

1 Ontology (Science) Barry Smith University at Buffalo

1 Introduction to (Geo)Ontology Barry Smith

1 The Ontology of Experiments Barry Smith

The Semantic Web Barry Smith

1 True Grid Barry Smith

Medical Ontologies: An Overview Barry Smith

1 Introduction to Ontology Barry Smith

Introduction to Ontologies for Environmental Biology Barry Smith

Framework for Formal Ontology Barry Smith and Kevin Mulliganontology.buffalo.edu/smith/articles/FormalOntology.pdf · 74 BARRY SMITH AND KEVIN MULLIGAN ample, that {unction, argument,

Barry Smith, Gestalt Theory

The Mouth Barry Smith

The Gene Ontology Barry Smith March 2004

1 Depicting Reality Barry Smith