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Forms of Life

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Title: Forms of Life


1
Forms of Life
Barry Smith http//ifomis.org
2
(No Transcript)
3
Scales of anatomy
Organism
Organ
Tissue
10-1 m
Cell
Organelle
10-5 m
Protein
DNA
10-9 m
4
New Golden Age of Classification
  • 30,000 genes in human
  • 200,000 proteins
  • 100s of cell types
  • 100,000s of disease types
  • 1,000,000s of biochemical pathways (including
    disease pathways)
  • legacy of Human Genome Project

5
FUNCTIONAL GENOMICS
  • proteomics,
  • reactomics,
  • metabonomics,
  • phenomics,
  • behaviouromics,
  • toxicopharmacogenomics

6
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?

7
Answer
  • Ontology

8
Google hits (as of yesterday)
  • ontology philosophy 143K
  • ontology engineering 145K
  • ontology information systems 217K
  • ontology software 252K
  • ontology database 279K

9
IFOMIS
  • Institute for Formal Ontology
  • and Medical Information Science

10
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 ?

11
A Linnaean Species Hierarchy
12
Medical Diagnostic Hierarchy
a hierarchy in the realm of diseases
13
Combining hierarchies
Organisms
Diseases
14
via Dependence Relations
Organisms
Diseases
15
A Window on Reality
16
A Window on Reality
Organisms
Diseases
17
A Window on Reality
18
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

19
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

20
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

21
Fragment of the UMLSemantic Network
22
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23
UMLS Semantic Network
  • entity event
  • physical conceptual
  • object entity
  • organism

24
conceptual entity
  • Organism Attribute
  • Finding
  • Idea or Concept
  • Occupation or Discipline
  • Organization
  • Group
  • Group Attribute
  • Intellectual Product
  • Language

25
  • Idea or Concept
  • Functional Concept
  • Qualitative Concept
  • Quantitative Concept
  • Spatial Concept
  • Body Location or Region
  • Body Space or Junction
  • Geographic Area
  • Molecular Sequence
  • Amino Acid Sequence
  • Carbohydrate Sequence
  • Nucleotide Sequence

26
Trattenbach
  • is an Idea or Concept

27
  • Idea or Concept
  • Functional Concept
  • Qualitative Concept
  • Quantitative Concept
  • Spatial Concept
  • Body Location or Region
  • Body Space or Junction
  • Geographic Area
  • Molecular Sequence
  • Amino Acid Sequence
  • Carbohydrate Sequence
  • Nucleotide Sequence

28
Problem Confusion of concepts and entities in
reality
29
Blood Pressure Ontology
  • The hydraulic equation
  • BP COPVR
  • arterial blood pressure (BP) is directly
    proportional to the product of blood flow
    (cardiac output, CO) and peripheral vascular
    resistance (PVR).

30
UMLS-Semantic Types
  • blood pressure is an Organism Function,
  • cardiac output is a Laboratory or Test Result or
    Diagnostic Procedure
  • BP COPVR thus asserts that
  • blood pressure is proportional either to a
    laboratory or test result or to a diagnostic
    procedure

31
Problem Confusion of reality with our (ways of
gaining) knowledge about reality
32
What are the terms of ontologies in the
ontological engineering sense
  • Answer Concepts

33
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

34
  • Trattenbach is_a class of synonymous terms

35
UMLS Semantic Network
  • entity
  • physical conceptual
  • object entity
  • organism

36
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)

37
  • fish is_a vertebrate
  • enzyme is_a biologically active substance
  • copulation is_a biological process

38
Fragment of the UMLSemantic Network
39
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40
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

41
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

42
  • 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

43
Fragment of the UMLSemantic Network
44
The Concept Orientation
  • Work on biomedical ontologies grew out of work on
    medical dictionaries and nomenclatures
  • Has 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.

45
Belnap
  • its a good thing logicians were around before
    computer scientists
  • if computer scientists had got there first,
    then we wouldnt have numbers
  • because arithmetic is undecidable

46
  • INSTANcES ARE SINGLETONS

47
  • Belnap
  • Hilbert's formalism is Kantianism (Cabalah)
    reference is one address writing to another
    addresses
  • molecules have their parts rigidly
  • 10 Billion Pounds for SNOMED
  • Influence of GO
  • Bad things in GO
  • Ontologies in BIO generally (google)
  • Functions, processes
  • Pancreas gene story
  • inhibition/function/regulation/plasticity/redundan
    cy/death
  • Evolution is opportunistic ( opportunistic
    infections) good for bacteria etc.
  • against Millikan -- cell death
  • life plan
  • physiology changes in qualities of parts
  • growth - getting bigger
  • development new kinds of things getting formed
  • aging involution
  • death

48
Aristotle-Linnaeus Theory of Species and Instances
49
species, genera
mammal
frog
instances
50
Husserls Science of Pure Logic
51
species, genera
a stands in R to something
mammal is P
a stands in R to b
instances
52
species, genera
a stands in R to something
mammal is P
a stands in R to b
LAWS OF LOGIC LAWS OF ESSENCE GOVERNING
STRUCTURES/COMBINATIONS OF JUDGMENT
53
The historical epistemology of the sciences
  • life-world
  • physics

medicine molecular biology
54
Different scientific cultures/terminologies
  • immunology

genetics
cell biology
55
(Quine)
  • an ontology is a systematic representation of
    the ontological commitments of a given scientific
    discipline, culture, commercial enterprise
  • childrens ontology
  • Buddhist ontology
  • wine ontology

56
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

57
Semantic Web
  • Ontology-based unification
  • REDUCE EVERYTHING TO SYNTACTIC STRINGS IN SOME
    Ontology Web Language
  • and STIR VIGOROUSLY
  • The Crisis of Bioinformatic Sciences

58
An alternative research programme for
ontologybased on philosophical principles
  • Department of Biological Structure (Seattle)
  • Ontek Corporation (Buffalo)
  • Laboratory for Applied Ontology (Trento/Rome)

59
BFO
  • Basic Formal Ontology
  • (counterpart of pure mathematics)

60
A Network of Domain Ontologies
Basic Formal Ontology
  • Material (Regional) Ontologies

61
A Network of Domain Ontologies
62
A Network of Domain Ontologies
63
Part Three ARO The Anatomy Reference Ontology
64
  • Anatomy Reference Ontology
  • theoretical framework surrounding the Digital
    Anatomist Foundational Model of Anatomy of
    Department of Biological Structure, University of
    Washington, Seattle

65
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66
A Linnaean Hierarchy
67
at every level of granularity
68
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.

69
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)

70
Part Four GO The Gene Ontology
71
GO is three ontologies
  • cellular components
  • molecular functions
  • biological processes
  • December 16, 2003
  • 1372 component terms
  • 7271 function terms
  • 8069 process terms

72
GO product of Open Biological Ontologies
consortium
  • Fungal Ontology
  • Plant Ontology
  • Yeast Ontology
  • Disease Ontology
  • ...

73
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?

74
GOs three ontologies
75
The Cellular Component Ontology (counterpart of
anatomy)
  • flagellum
  • chromosome
  • membrane
  • cell wall
  • nucleus

76
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

77
Biological Process Ontology
  • Examples
  • glycolysis
  • death
  • adult walking behavior
  • response to blue light
  • occurrents on the level of granularity of
    cells, organs and whole organisms

78
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

79
but GO built by biologists
  • compare the Gene Statistic

80
hemolysis
  • Definition
  • The cause of hemolysis

81
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.

82
Biological Process
  • Definition
  • A biological process is a biological goal that
    requires more than one function. Mutant
    phenotypes often reflect disruptions in
    biological processes.

83
Each of GOs 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)

84
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85
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 dont
    know
  • Holliday junction helicase complex
  • is-a
  • unlocalized

86
GO0008372 cellular component unknown cellular
component unknown is-a cellular component
87
Is biological classification Linnaean?
88
Principle of Single Inheritance
  • no class in a true (Linnaean) hierarchy should
    have more than one parent on the immediate higher
    level
  • no diamonds

89
Problems with multiple inheritance
  • B C
  • is-a1 is-a2
  • A
  • is-a no longer univocal

90
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

91
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

92
extrinsic to
  • extrinsic to membrane
  • extrinsic to membrane part-of membrane

93
GOs three ontologies are separate
biological processes
molecular functions
  • No links or edges defined between them

cellular components
94
Three granularities
  • Molecular (for functions)
  • Cellular (for components)
  • Whole organism (for processes)

95
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)

96
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

97
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

98
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99
Part Five
  • Extending GO to make a full ontology by adding
    relations of dependence

100
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

101
Principle of Dependence
  • If an ontology recognizes a dependent entity
    then it (or a linked ontology) should recognize
    also the relevant class of bearers

102
Linking to external ontologies
  • can also help to link together GOs own three
    separate parts

103
GOs three ontologies
biological processes
molecular functions
? dependent ?
cellular components
? independent
104
GOs three ontologies
organism-level biological processes
cellular processes
molecular functions
cellular components
105
molecular functions
cellular processes
organism-level biological processes
molecule complexes
cellular components
organisms
part-of is dependent
on
106
molecule complexes
cellular components
organisms
107
molecule complexes
cellular components
organisms
108
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

109
  • The End

110
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

111
Organism
Organ
Tissue
Cell
Organelle
Protein
DNA
112
The Challenge
  • Each (clinical, pathological, genetic,
    proteomic, pharmacological ) information system
    uses its own terminology and category system
  • biomedical 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?

113
Answer
  • Ontology

114
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

115
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

116
Formal ontology an analogue of pure mathematics
  • Can be applied to different domains

117
Material ontology a kind of generalized chemistry
or zoology
  • (Aristotles ontology grew out of biological
    classification)

118
Aristotle
worlds first ontologist

119
Worlds first ontology (from Porphyrys
Commentary on Aristotles Categories)
120
Linnaean Ontology
121
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

122
Formal Ontology
  • the theory of those ontological structures
  • (such as part-whole, universal-particular)
  • which apply to all domains whatsoever

123
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

124
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)

125
Formal-Ontological Categories
  • substance
  • process
  • function
  • unity
  • plurality
  • site
  • dependent part
  • independent part
  • are able to form complex structures in
    non-arbitrary ways joined by relations such as
    part, dependence, location.

126
Example of a Formal-Ontological Structure
A
B
C
E
D
127
Ontological Structure
A
B
C
E
D
128
Ontological Structure
A
B
F
C
E
D
129
A Network of Domain Ontologies
Basic Formal Ontology
  • Material (Regional) Ontologies

130
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

131
Material Ontology of Social Interaction
oblig-ation
claim
132
A Window on Reality
133
Universals
oblig-ation
claim
134
Instances
oblig-ation
claim
135
A Window on Reality
136
Medical Diagnostic Hierarchy
a hierarchy in the realm of diseases
137
Dependence Relations
Organisms
Diseases
138
A Window on Reality
Organisms
Diseases
139
A Window on Reality
140
universals
mammal
frog
instances
141
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142
(No Transcript)
143
Many current standard ontologies ramshackle
because they have no counterpart of formal
ontology
  • The Universal Medical Language System (UMLS)
  • a compendium of source vocabularies including
  • HL7 RIM
  • SNOMED
  • International Classification of Diseases
  • MeSH Medical Subject Headings
  • Gene Ontology

144
Problem The different source vocabularies are
incompatible with each other
145
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

146
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

147
Bad definitions
  • Heptolysis def the cause of heptolysis
  • Biological process def a biological goal that
    requires more than one function

148
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

149
correct reading of is-a
  • A and B are natural kinds,
  • there are times at which instances of A exist,
  • 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

150
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)

151
Instances are elite individuals
  • they are those which instantiate universals
    (entering into biological laws)

152
Linnaean Ontology
153
Confusion of Ontology and Epistemology
  • Physical Object
  • Substance
  • Food Chemical Body Substance

154
Confusion of Ontology and Epistemology
  • Chemical
  • Chemical Chemical
  • Viewed Viewed
  • Structurally Functionally

155
  • Chemical
  • Chemical Chemical
  • Viewed Viewed
  • Structurally Functionally
  • Inorganic Organic Enzyme
    Biomedical or
  • Chemical Chemical Dental
    Material

156
  • Chemical
  • Chemical Chemical
  • Viewed Viewed
  • Structurally Functionally
  • Inorganic Organic
    Biomedical or
  • Chemical Chemical Dental
    Material

Enzyme
157
Is biological classification Linnaean?
158
Principle of Single Inheritance
  • (rule of thumb) no class in a classificatory
    hierarchy should have more than one parent

159
The Problem of Multiple Inheritance
  • cars
  • Buicks blue cars
  • blue Buicks

160
Principle of Taxonomic Levels

161
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 GOs hierarchies not determinate
    because of multiple inheritance

162
Principle of Exhaustiveness
  • the classes on any given level should exhaust
    the domain of the classificatory hierarchy.

163
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

164
Problems with multiple inheritance
  • B C
  • is-a1
    is-a2
  • A
    E
  • D
  • sibling is no longer determinate

165
Problems with multiple inheritance
  • B C
  • is-a1
    is-a2
  • A
    E
  • D
  • is_a is no longer univocal

166
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

167
How are universals and instances related together?
168
Entities
169
Entities
universals (classes, types, taxa, )
particulars (individuals, tokens, instances )
Axiom Nothing is both a universal and a
particular
170
Two Kinds of Elite Entities
  • classes, within the realm of universals
  • instances within the realm of particulars

171
Entities
classes
172
Entities
classes natural, biological
173
Entities
classes of objects, substances need
modified axioms for classes of functions,
processes, pathways, reactions, etc.
174
Entities
classes
instances
175
Classes are natural kinds
  • Instances are natural exemplars of natural kinds
  • (problem of non-standard instances)
  • Not all individuals are instances of classes

176
Entities
classes
instances
instances
177
Entities
classes
junk
junk
instances
junk
example of junk beachball-desk
178
Primitive relations inst and part
  • inst(Jane, human being)
  • part(Janes heart, Janes body)
  • A class is anything that is instantiated
  • An instance as anything (any individual) that
    instantiates some class

179
Entities
human
inst
Jane
180
Entities
human
Janes heart part Jane
181
part as a relation between individuals
  • subject to the usual axioms of mereology

182
Two primitive relations inst and part
  • inst(Jane, human being)
  • part(Janes heart, Janes body)
  • A universal is anything that is instantiated
  • An instance is anything (any individual) that
    instantiates some class

183
Two primitive relations inst and part
  • Axioms governing inst
  • it holds in every case between an instance and a
    class, in that order
  • 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)

184
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.

185
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.

186
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

187
if they can be cleared up at all
188
Fragment of the UMLSemantic Network
189
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190
  • Mental Process precedes Molecular Function
  • Mental Process precedes Genetic Function
  • Experimental Model of Disease precedes Cell or
    Molecular Dysfunction
  • Acquired Abnormality affects Bird
  • Experimental Model of Disease affects Fungus
  • Physiologic Function affects Reptile
  • Antibiotic 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
  • Fungus location_of Vitamin
  • Organization location_of Diagnostic Procedure

191
What are universals?
  • invariants in reality
  • satisfying biological laws
  • (there are truths about universals in biological
    textbooks)

192
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)

193
Universals are Not Sets
  • Both universals and sets are marked by
    granularity but universals are timeless
  • Both 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.

194
  • 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)

195
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.

196
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197
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 ?

198
Towards an Tri-Categorial Ontology
  • of Structures, Functions and Processes

199
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

200
The Kidney From Andrew Lonie, University of
Melbourne
Your entire blood volume flows through your
kidneys every few minutes, leaving behind excess
water, solutes and waste materials
201
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
202
Nephron Functions
10 functional segments
15 different cell types
203
Structural and functional representation
Structural ontology Kidney Renal
architecture Tubule section/ Glomerulus Cell
ANATOMY AT DIFFERENT LEVELS OF GRANULARITY
process ontology (molecular, cellular,
organ-level )
204
UMLS Semantic Network
  • entity event
  • physical conceptual
  • object entity
  • organism

205
Tri-Categorial Ontology present also in GO The
Gene Ontology
  • 3 ontologies (large telephone directories) of
    standardized designations for gene functions and
    products

206
RUMLS Semantic Network
  • entity event
  • structures functions processes

207
GOs 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

208
RUMLS Semantic Network
  • entity event
  • structures functions processes

209
Functional Genomics
  • What does Functional mean?

210
The Problem
  • The tumor developed in Johns lung over 25 years

211
The Problem
  • ____ developed in _____ over 25 years
  • process

212
The Problem
  • The tumor developed in the lung over 25 years
  • substances
  • things
  • objects
  • continuants

213
The Problem
  • The tumor developed in Johns lung over 25 years
  • PARTHOOD NOT DETERMINATE

214
The Problem
  • The tumor developed in the lung over 25 years
  • substances
  • GLUING THESE TOGETHER YIELDS ONTOLOGICAL MONSTERS

215
Substances and processes exist in time in
different ways
substance
216
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

217
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

218
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

219
Fourdimensionalism (the SPAN perspective) is
right in everything it says
  • But incomplete

220
Need for Two Orthogonal, Complementary
Perspectives
SNAP and SPAN
221
Snapshot Video ontology
ontology
substance
222
SNAP and SPAN
  • stocks and flows
  • commodities and services
  • product and process
  • anatomy and physiology

223
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

224
You are a substance
  • Your life is a process
  • You are 3-dimensional
  • Your life is 4-dimensional

225
Many SNAP Ontologies
t3
t2
t1
here time exists outside the ontology, as an
index or time-stamp
226
each SNAPi section through reality
227
mereology works without restriction (parthood is
everywhere determinate) in every SNAPi ontology
228
Three kinds of SNAP entities
  1. SNAP Independent Entities (you and me)
  2. SNAP Dependent Entities
  3. Spatial regions

229
SNAP dependent entities
  • States, powers, qualities, functions,
    dispositions, plans, shapes, liabilities,
    propensities

230
SNAP dependent entities
  • one-place
  • your temperature, color, height
  • my knowledge of French
  • the whiteness of this cheese
  • the warmth of this stone
  • the fragility of this glass

231
  • relational SNAP dependent entities

stand in relations of one-sided dependence to a
plurality of substances simultaneously
one-sided dependence
232
A Window on Reality
233
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

234
SNAP Entities existing in toto at a time
http//ontology.buffalo.edu/bfo
235
The SPAN Ontology
236
The SPAN ontology
here time exists as part of the domain of the
ontology
237
mereology works without restriction everywhere
here
238
mereology works without restriction everywhere
here
239
Processes, too, are dependent on substances
  • One-place vs. relational processes
  • One-place processes
  • your getting warmer
  • your getting hungrier

240
Relational processes
  • kissings, thumpings, conversations,
  • dancings, promisings, infectings, bindings
  • join their carriers together into collectives of
    greater or lesser duration

241
SPAN Entities extended in time
http//ontology.buffalo.edu/bfo
242
Two kinds of SPAN entities
  1. Processes (including events process-boundaries,
    settings)
  2. Spatio-temporal regions

243
How do you know whether an entity is SNAP or SPAN?
244
problem cases
  • forest fire
  • hurricane Maria
  • traffic jam
  • ocean wave
  • disease
  • anthrax epidemic

245
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)

246
A disease
  • The course/history of a disease

247
The Epidemic (SNAP)
  • The Spread of an Epidemic (SPAN)

248
Material examples
  • performance of a symphony
  • projection of a film
  • expression of an emotion
  • utterance of a sentence
  • application of a therapy
  • increase of temperature

249
The Tri-Categorial Ontology
  • SNAP SPAN
  • structures functions processes
  • independent dependent
  • continants continuants

250
The Tri-Categorial Ontology
  • continuants occurrents
  • structures functions processes
  • independent dependent
  • continants continuants

251
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 blood
  • The function of my heart is to pump blood

252
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

253
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 )

254
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)

255
Functions can exist even when they are not being
realized
256
Processes (realizations) are causal-energetic


  • time

257
Functions are historical (they exist in time)
but they are also quasi-Platonic


  • time

258
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

259
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

260
Biological functions are always constituent
functions
  • If X has a biological function then there is some
    Y of which X is a part and Xs functioning is in
    the service of / for the benefit of Y

261
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)

262
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)

263
Does this sense of function correspond to the
way biologists talk?
264
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?

265
Health Disease Illness
  • Diseased organ organ predisposed to malfunction
  • Its functioning is defective

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267
Part Four Definitions of Health
  • World Health Organization
  • Health is the state of psychological and
    physical well-being of humans

268
Biostatistical TheoryChristopher Boorse
  • Health is conformity to normal species design (as
    statistically determined).
  • Abnormally healthy people are therefore in fact
    sick (?)

269
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 persons body
    or mind that tends to cause ill health in the
    bearer.

270
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.

271
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 circumstancessomething does a person
    harm if it makes the person less able to live a
    good or worthwhile life.

272
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

273
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

274
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

275
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

276
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

277
Diseases are both historical and quasi-Platonic


  • time

278
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

279
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

280
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

281
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282
Outside the core
  • are process shapes which are not instances of
    functioning at all

283
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284
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285
Normal functioning
  • functioning (realizing a four-dimensional
    shape) at or close to the prototype

286
Prototypes
good functioning
287
Prototypes
reasonable functioning
288
Poor functioning
poor functioning
289
Malfunctioning
malfunctioning
290
Death?
not functioning at all
291
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

292
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

293
Millikan backward looking, focused on whole
species
  • This account forward looking, focused on single
    organism
  • X has a function (1) Xs functioning is
    beneficial to the organism of which X is a part

294
Boorses Internal Impairment Theory
  • Disease is an internal state which is an
    impairment or limitation of normal functional
    ability.

295
Disease
296
Disease remoteness from prototypical functioning
disease
297
Disease remoteness from prototypical functioning
1 not functioning at all 2 malfunctioning 3
functioning poorly
1 2 3
disease
298
Not functioning at all
  • death modulo
  • criticality of the system involved

299
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

300
Immediate parts of the organism are more critical
301
Bodily Systems
digestive
respiratory
circulatory
immune
skeletal
musculatory
302
ENDOCRINE SYSTEM
303
KIDNEY
304
How does a kidney work?
NEPHRON
305
Nephron Functions
FUNCTIONAL SEGMENTS
306
Organism
Organ
Tissue
Cell
Organelle
Protein
DNA
307
Coda on Normal
  • Normal functioning of the pancreas
  • Normal functioning of the sexual organs
  • On the several senses of normal in biology

308
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

309
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

310
  • The End
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