1 Forms of Life Barry Smith . 2.
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Forms of Life
Barry Smith
http://ifomis.org
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DNA
Protein
Organelle
Cell
Tissue
Organ
Organism
10-5 m
10-1 m
Scales of anatomy
10-9 m
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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
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FUNCTIONAL GENOMICS
proteomics,
reactomics,
metabonomics,
phenomics,
behaviouromics,
toxicopharmacogenomics
…
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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?
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Answer:
“Ontology”
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Google hits (as of yesterday)
ontology + philosophy 143K
ontology + engineering 145K
ontology + information systems 217K
ontology + software 252K
ontology + database 279K
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IFOMIS
Institute for Formal Ontology
and Medical Information Science
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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 ?
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A Linnaean Species Hierarchy
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Medical Diagnostic Hierarchy
a hierarchy in the realm of diseases
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Combining hierarchies
Organisms Diseases
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via Dependence Relations
Organisms Diseases
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A Window on Reality
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A Window on Reality
Organisms Diseases
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A Window on Reality
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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
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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
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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
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21Fragment of the UMLSemantic Network
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UMLS Semantic Network
entity event
physical conceptual object entity
organism
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conceptual entity
Organism Attribute
Finding
Idea or Concept
Occupation or Discipline
Organization
Group
Group Attribute
Intellectual Product
Language
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Idea or ConceptFunctional ConceptQualitative ConceptQuantitative ConceptSpatial Concept
Body Location or RegionBody Space or JunctionGeographic AreaMolecular Sequence
Amino Acid SequenceCarbohydrate SequenceNucleotide Sequence
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Trattenbach
is an Idea or Concept
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Idea or ConceptFunctional ConceptQualitative ConceptQuantitative ConceptSpatial Concept
Body Location or RegionBody Space or JunctionGeographic AreaMolecular Sequence
Amino Acid SequenceCarbohydrate SequenceNucleotide Sequence
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Problem: Confusion of concepts and entities in reality
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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).
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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
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Problem: Confusion of reality with our (ways of gaining) knowledge
about reality
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What are the terms of ontologies in the ontological engineering sense
Answer: Concepts
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‘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
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Trattenbach is_a class of synonymous terms
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UMLS Semantic Network
entity
physical conceptual object entity
organism
is_a
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is_a
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)
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fish is_a vertebrate
enzyme is_a biologically active substance
copulation is_a biological process
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38Fragment of the UMLSemantic Network
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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
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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
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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
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43Fragment of the UMLSemantic Network
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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.
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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”
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INSTANcES ARE SINGLETONS
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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
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Aristotle-Linnaeus Theory of Species and Instances
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siamese
mammal
cat
organism
substancespecies, genera
animal
instances
frog
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Husserl’s Science of Pure Logic
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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
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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
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The historical epistemology of the sciences
life-world
physics
medicine
molecular biology
granularity
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Different scientific cultures/terminologies
immunology
genetics
cell biology
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(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
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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
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Semantic Web
Ontology-based unification =
REDUCE EVERYTHING TO SYNTACTIC STRINGS IN SOME ‘Ontology Web Language’
and STIR VIGOROUSLY
The Crisis of Bioinformatic Sciences
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An alternative research programme for ontology
based on philosophical principles
Department of Biological Structure (Seattle)
Ontek Corporation (Buffalo)
Laboratory for Applied Ontology (Trento/Rome)
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Basic Formal Ontology
(counterpart of pure mathematics)
BFO
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A Network of Domain Ontologies
Material (Regional) Ontologies
Basic Formal Ontology
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A Network of Domain Ontologies
BFO
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A Network of Domain Ontologies
PsychO
GO ARO
PhysiO
ChemO
BFO
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Part ThreeARO: The Anatomy Reference Ontology
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Anatomy Reference Ontology =
theoretical framework surrounding the Digital Anatomist Foundational Model of Anatomy of Department of Biological Structure, University of Washington, Seattle
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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
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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
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at every level of granularity
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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.”
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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)
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Part Four
GO: The Gene Ontology
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GO is three ontologies
cellular componentsmolecular functions biological processes
December 16, 2003:1372 component terms7271 function terms8069 process terms
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GO product of Open Biological Ontologies consortium
Fungal Ontology
Plant Ontology
Yeast Ontology
Disease Ontology
...
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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?
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GO’s three ontologies
molecular functions
cellular components
biological processes
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The Cellular Component Ontology (counterpart of anatomy)
flagellum
chromosome
membrane
cell wall
nucleus
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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
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Biological Process Ontology
Examples:glycolysisdeathadult walking behaviorresponse to blue light
= occurrents on the level of granularity of cells, organs and whole organisms
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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
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but: GO built by biologists
compare: the Gene Statistic
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hemolysis
Definition
The cause of hemolysis …
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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.
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Biological Process
Definition:
A biological process is a biological goal that requires more than one function. Mutant phenotypes often reflect disruptions in biological processes.
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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)
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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
is-a
unlocalized
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GO:0008372 cellular component unknown
cellular component unknown is-a cellular component
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Is biological classification Linnaean?
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Principle of Single Inheritance
no class in a true (Linnaean) hierarchy should have more than one parent on the immediate higher level
no diamonds:
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Problems with multiple inheritance
B C
is-a1 is-a2
A
‘is-a’ no longer univocal
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‘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
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‘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
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‘extrinsic to’
extrinsic to membrane
extrinsic to membrane part-of membrane
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GO’s three ontologies are separate
No links or edges defined between them
molecular functions
cellular components
biological processes
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Three granularities:
Molecular (for functions)
Cellular (for components)
Whole organism (for processes)
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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)
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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
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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
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Part Five
Extending GO to make a full ontology by adding relations of dependence
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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
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Principle of Dependence
If an ontology recognizes a dependent entity then it (or a linked ontology) should recognize also the relevant class of bearers
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Linking to external ontologies
can also help to link together GO’s own three separate parts
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GO’s three ontologies
molecular functions
cellular components
biological processes
dependent
independent
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GO’s three ontologies
molecular functions
cellular components
organism-level
biological processes
cellularprocesses
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molecular functions
moleculecomplexe
s
cellularprocesses
cellular components
organism-level
biological processes
organisms
‘part-of’; ‘is dependent on’
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moleculecomplexe
s
cellular component
s
molecular function
s
cellularfunctions
organism-level
biological functions
organisms
molecular processe
s
cellularprocesses
organism-level
biological processes
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moleculecomplexe
s
cellular component
s
molecular function
s
cellularfunctions
organism-level
biological functions
organisms
molecular processe
s
cellularprocesses
organism-level
biological processes
functioningsfunctionings functionings
junk processes
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Basic Formal Ontology
– 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
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The End
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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
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DNA
Protein
Organelle
Cell
Tissue
Organ
Organism
Muscle tissueNerve tissueConnective tissueEpithelial tissueBlood
Musculo-skeletal systemCirculatory systemRespiratory systemDigestive systemNervous systemUrinary systemReproductive systemEndocrine systemLymphoidal system
MitochondriaNucleusEndoplasmic reticulumCell membrane
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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?
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Answer:
“Ontology”
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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
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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
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Formal ontology an analogue of pure mathematics
Can be applied to different domains
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Material ontology a kind of generalized chemistry or zoology
(Aristotle’s ontology grew out of biological classification)
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Aristotle
world’s first ontologist
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World‘s first ontology
(from Porphyry’s Commentary on Aristotle’s Categories)
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Linnaean Ontology
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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
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Formal Ontology
the theory of those ontological structures
(such as part-whole, universal-particular)
which apply to all domains whatsoever
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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
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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)
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Formal-Ontological Categoriessubstanceprocessfunctionunitypluralitysitedependent partindependent part
are able to form complex structures in non-arbitrary ways joined by relations such as part, dependence, location.
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Example of a Formal-Ontological Structure
D E
A BC
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Ontological Structure
D E
A BC
two-sided mutual dependence
one-sided dependence
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Ontological Structure
D E
A B
C
part-whole
relation
F
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A Network of Domain Ontologies
Material (Regional) Ontologies
Basic Formal Ontology
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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
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Material Ontology of Social Interaction
oblig-ation
claim
promiser
promisee
act of speaking
act of registering
content
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A Window on Reality
oblig-ation
claim
promiser
promisee
act of speaking
act of registering
content
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Universals
oblig-ation
claim
promiser
promisee
act of speaking
act of registering
content
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Instances
oblig-ation
claim
promiser
promisee
act of speaking
act of registering
content
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A Window on Reality
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Medical Diagnostic Hierarchy
a hierarchy in the realm of diseases
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Dependence Relations
Organisms Diseases
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A Window on Reality
Organisms Diseases
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A Window on Reality
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siamese
mammal
cat
organism
substanceuniversals
animal
instances
frog
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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
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Problem: The different source vocabularies are incompatible with
each other
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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
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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
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Bad definitions
Heptolysis =def the cause of heptolysis
Biological process =def a biological goal that requires more than one function
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is-a
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
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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
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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)
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Instances are elite individuals
they are those which instantiate universals (entering into biological laws)
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Linnaean Ontology
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Confusion of Ontology and Epistemology
Physical Object
Substance
Food Chemical Body Substance
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Confusion of Ontology and Epistemology
Chemical
Chemical Chemical
Viewed Viewed
Structurally Functionally
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Chemical
Chemical ChemicalViewed Viewed
Structurally Functionally
Inorganic Organic Enzyme Biomedical or Chemical Chemical Dental Material
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Chemical
Chemical Chemical
Viewed Viewed
Structurally Functionally
Inorganic Organic Biomedical or
Chemical Chemical Dental Material
Enzyme
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Is biological classification Linnaean?
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Principle of Single Inheritance
(rule of thumb) no class in a classificatory hierarchy should have more than one parent
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The Problem of Multiple Inheritance
cars
Buicks blue cars
blue Buicks
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Principle of Taxonomic Levels
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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
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Principle of Exhaustiveness
the classes on any given level should exhaust the domain of the classificatory hierarchy.
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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
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Problems with multiple inheritance
B C
is-a1 is-a2
A E
D
‘sibling’ is no longer determinate
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Problems with multiple inheritance
B C
is-a1 is-a2
A E
D
‘is_a’ is no longer univocal
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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
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How are universals and instances related together?
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Entities
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Entities
universals (classes, types, taxa, …)
particulars (individuals, tokens, instances …)
Axiom: Nothing is both a universal and a particular
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Two Kinds of Elite Entities
classes, within the realm of universals
instances within the realm of particulars
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Entities
classes
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Entities
classes*
*natural, biological
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Entities
classes of objects, substances
need modified axioms for classes of functions, processes, pathways, reactions, etc.
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Entities
classes
instances
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Classes are natural kinds
Instances are natural exemplars of natural kinds
(problem of non-standard instances)
Not all individuals are instances of classes
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Entities
classes
instancesinstances
penumbra of borderline cases
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Entities
classes
instances
junkjunk
junk
example of junk: beachball-desk
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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
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Entities
human
Jane
inst
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Entities
human
Jane’s heart part Jane
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part as a relation between individuals
subject to the usual axioms of mereology
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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
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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)
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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.
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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.
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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
etc.
Reference to instances is necessary to clear up these problems
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if they can be cleared up at all …
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188Fragment of the UMLSemantic Network
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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
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What are universals?
invariants in reality
satisfying biological laws(there are truths about universals in
biological textbooks)
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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)
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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.
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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)
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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.
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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” ?
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Towards an Tri-Categorial Ontology
of Structures, Functions and Processes
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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
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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
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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
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Nephron Functions
10 functional segments15 different cell types
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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 …)
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UMLS Semantic Network
entity event
physical conceptual object entity
organism
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Tri-Categorial Ontology present also in GO: The Gene Ontology
3 ‘ontologies’ (large telephone directories) of standardized designations for gene functions and products
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RUMLS Semantic Network
entity event
structures functions processes
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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
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RUMLS Semantic Network
entity event
structures functions processes
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Functional Genomics
What does “Functional“ mean?
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The Problem
The tumor developed in John’s lung over 25 years
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The Problem
____ developed in _____ over 25 years
process
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The Problem
The tumor developed in the lung over 25 years
substances
things
objects
continuants
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The Problem
The tumor developed in John’s lung over 25 years
PARTHOOD NOT DETERMINATE
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The Problem
The tumor developed in the lung over 25 years
substances
GLUING THESE TOGETHER YIELDS ONTOLOGICAL MONSTERS
processes
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Substances and processes exist in time in different ways
substance
t i m
e
process
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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
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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
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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
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Fourdimensionalism (the SPAN perspective) is right in
everything it says
But incomplete
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Need for Two Orthogonal, Complementary Perspectives
SNAP and SPAN
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Snapshot Video ontology ontology
substance
t i m
e
process
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SNAP and SPAN
stocks and flows
commodities and services
product and process
anatomy and physiology
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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
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You are a substance
Your life is a process
You are 3-dimensional
Your life is 4-dimensional
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Many SNAP Ontologies
t1
t3
t2
here time exists outside the ontology, as an index or time-stamp
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each SNAPi section through reality
includes everything which exists (present tense)
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mereology works without restriction (parthood is everywhere determinate) in
every SNAPi ontology
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Three kinds of SNAP entities
1. SNAP Independent Entities (you and me)
2. SNAP Dependent Entities
3. Spatial regions
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SNAP dependent entities
States, powers, qualities, functions, dispositions, plans, shapes, liabilities,
propensities…
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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
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relational SNAP dependent entities
John Mary
love
stand in relations of one-sided dependence to a plurality of substances simultaneously
one-sided dependence
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A Window on Reality
oblig-ation
claim
promiser
promisee
act of speaking
act of registering
content
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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
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SNAP: Entities existing in toto at a time
http://ontology.buffalo.edu/bfo
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The SPAN Ontology
t i m e
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here time exists as part of the domain of the ontology
The SPAN ontology
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mereology works without restriction everywhere here
t i m e
clinical trial
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mereology works without restriction everywhere here
t i m e
course of a disease
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Processes, too, are dependent on substances
One-place vs. relational processes
One-place processes:
your getting warmer
your getting hungrier
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Relational processes
kissings, thumpings, conversations,
dancings, promisings, infectings, bindings
join their carriers together into collectives of greater or lesser duration
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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
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Two kinds of SPAN entities
1. Processes (including events: process-boundaries, settings)
2. Spatio-temporal regions
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How do you know whether an entity is SNAP or SPAN?
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problem cases
forest fire
hurricane Maria
traffic jam
ocean wave
disease
anthrax epidemic
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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)
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A disease
The course/history of a disease
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The Epidemic (SNAP)
The Spread of an Epidemic (SPAN)
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Material examples:
performance of a symphonyprojection of a filmexpression of an emotionutterance of a sentenceapplication of a therapyincrease of temperature
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The Tri-Categorial Ontology
SNAP SPAN
structures functions processes= independent = dependent continants continuants
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The Tri-Categorial Ontology
continuants occurrents
structures functions processes= independent = dependent continants continuants
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A Window on Reality
continuants occurrents
structures functions processes= independent = dependent continants continuants
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
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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
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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 …)
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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)
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Functions can exist even when they are not being realized
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Processes (realizations) are causal-energetic
time
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Functions are historical (they exist in time)
but they are also quasi-Platonic
time
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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
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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
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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
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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)
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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)
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Does this sense of ‘function’ correspond to the way biologists talk?
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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?
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Health – Disease – Illness
Diseased organ = organ predisposed to malfunction
Its functioning is defective
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Part Four: Definitions of Health
World Health Organization:
Health is the state of psychological and physical well-being of humans
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Biostatistical TheoryChristopher Boorse
Health is conformity to normal species design (as statistically determined).
Abnormally healthy people are therefore in fact sick (?)
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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.
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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.
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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.
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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
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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
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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
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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
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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
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Diseases are both historical and quasi-Platonic
time
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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 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
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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
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Outside the core
are process shapes which are not instances of functioning at all
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Normal functioning
= functioning (realizing a four-dimensional shape) at or close to the prototype
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Prototypes
good functioning
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Prototypes
reasonable functioning
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Poor functioning
poor functioning
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Malfunctioning
malfunctioning
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Death?
not functioning at all
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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
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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
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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
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Boorse’s Internal Impairment Theory
Disease is an internal state which is an impairment or limitation of normal functional ability.
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Disease
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Disease = remoteness from prototypical functioning
disease
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Disease = remoteness from prototypical functioning
disease
1 2 3 1 = not functioning at all
2 = malfunctioning
3 = functioning poorly
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Not functioning at all
= death modulo:
criticality of the system involved
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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
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Immediate parts of the organism are more critical
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Bodily Systems
respiratorydigestive skeletal circulatorymusculatory immune
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ENDOCRINE
SYSTEM
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What do the kidneys do?KIDNEY
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How does a kidney work?NEPHRON
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Nephron FunctionsFUNCTIONAL SEGMENTS
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DNA
Protein
Organelle
Cell
Tissue
Organ
Organism
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Coda on ‘Normal’
Normal functioning of the pancreas
Normal functioning of the sexual organs
On the several senses of ‘normal’ in biology
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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
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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 …
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The End