The Future of Disease Ontology - PowerPoint PPT Presentation

Loading...

PPT – The Future of Disease Ontology PowerPoint presentation | free to download - id: 3bda32-NjM4M



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

The Future of Disease Ontology

Description:

The Future of Disease Ontology Barry Smith Department of Philosophy, University at Buffalo National Center for Biomedical Ontology http://ontology.buffalo.edu/smith – PowerPoint PPT presentation

Number of Views:63
Avg rating:3.0/5.0
Slides: 152
Provided by: ontologyB
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: The Future of Disease Ontology


1
The Future of Disease Ontology
  • Barry Smith
  • Department of Philosophy, University at Buffalo
  • National Center for Biomedical Ontology
  • http//ontology.buffalo.edu/smith

2
Colors form a continuum
3
colors form a prototyped continuum
4
strategy of low hanging fruitfocus on the
foci(cross-cultural, lexicalized)
5
Strategies for creating ontologies and
terminologies
  • Ad hoc creation by each clinical or research
    community (à la UMLS)
  • versus
  • Coordinated creation of high quality reference
    ontologies in ways which serve reusability of
    clinical data and interoperability of with basic
    science
  • Ontologies as common railway gauge

6
A simple rule
  • Use singular nouns
  • Disease
  • Diseases
  • Disorder
  • Disorders
  • disorder
  • disease
  • disorders
  • diseases

7
Which strategy is more future proof?
  • Assumption As time goes by the
    molecular/cellular basis of diseases will play an
    ever more important role in clinical medicine

8
OBO Foundry
  • A subset of OBO ontologies whose developers
    agree in advance to accept a common set of
    principles designed to assure interoperability
    with basic science and support for logic-based
    reasoning
  • http//obofoundry.org

9
OBO Foundry
  • Gene Ontology
  • Cell Ontology
  • Sequence Ontology
  • RNA Ontology
  • PATO Phenotype Ontology
  • OBI Ontology of Biomedical Investigations (née
    FuGO Functional Genomics Investigation Ontology)
  • FMA
  • RO Relation Ontology

10
GOs three ontologies
continuant
occurrent
biological process
cellular component
molecular function
11
Building out fron the original GO
12
  • The ontology is open and available to be used by
    all.
  • The developers of the ontology agree in advance
    to collaborate with developers of other OBO
    Foundry ontology where domains overlap.
  • The ontology is in, or can be instantiated in, a
    common formal language.
  • The ontology possesses a unique identifier space
    within OBO.
  • The ontology provider has procedures for
    identifying distinct successive versions.

13
  • The ontology has a clearly specified and clearly
    delineated content.
  • The ontology includes textual definitions for all
    terms.
  • The ontology is well-documented.
  • The ontology has a plurality of independent
    users.
  • The ontology uses relations which are
    unambiguously defined following the pattern of
    definitions laid down in the OBO Relation
    Ontology.

14
ORTHOGONALITY
  • The developers commit to working with other
    Foundry members to ensure community convergence
    on a single controlled vocabulary for each
    domain.
  • REASON if we annotate a database or body of
    literature with one high-quality biomedical
    ontology, we should be able to add annotations
    from a second such ontology without conflicts
  • INTEGRATION PRESUPPOSES ADDITIVITY

15
(No Transcript)
16
Goal when we annotate disease-related data
  • the disease terms we use should yield
    annotations which are logically consistent with
    and even inferable from other annotations using
    other OBO Foundry ontologies

17
Foundational Model of Anatomy (FMA)
  • ontology of structural human anatomy

18
FMA
  • organized in a graph-theoretical structure
    involving two sorts of links or edges
  • is-a ( is a subtype of )
  • (pleural sac is-a serous sac)
  • part-of
  • (cervical vertebra part-of vertebral column)

19
Anatomical Space
Anatomical Structure
Organ Cavity Subdivision
Organ Cavity
Organ
Serous Sac
Organ Component
Serous Sac Cavity
Tissue
Serous Sac Cavity Subdivision
is_a
Pleural Sac
Pleura(Wall of Sac)
Pleural Cavity
part_of
Parietal Pleura
Visceral Pleura
Interlobar recess
Mediastinal Pleura
Mesothelium of Pleura
20
FMA follows formal rules for Aristotelian
definitions
  • When A is_a B, the definition of A takes the
    form
  • an A Def. a B which C s...
  • a human being Def. an animal which is rational

21
Example
  • Cell Def. an anatomical structure which consists
    of cytoplasm surrounded by a plasma membrane

22
at every level of granularity
23
The Gene Ontology
  • Cross-Species
  • Cross-Granularity
  • Impressive policies for maintenance
  • Has initiated logic-based reforms
  • relations to other ontologies
  • relations among GOs 3 ontologies
  • Aristotelian definitions
  • enhanced treatment of granularity

24
Multiple Inheritance
  • thing

car
blue thing
is_a
is_a
blue car
25
Multiple Inheritance
  • thing

blue thing
car
is_a1
is_a2
blue car
26
is_a Overloading
  • Reasoning across ontologies demands that
    ontological relations (is_a, part_of, ...) have
    the same meanings in the different ontologies to
    be aligned.

27
Multiple Inheritance
  • thing

color
is_a
is_a
car
blue
is_a
car 2947 is blue
dark blue
28
Multiple Inheritance
  • fracture

anatomical structure
is_a
is_a
spiral fracture
limb
is_a
leg 29 has fracture 12
leg
29
Multiple Inheritance
  • pharyngitis

anatomical structure
is_a
is_a
heterogeneous cluster
infectious pharyngitis
is_a
disease instance 12 inheres in pharynx 29
pharynx
30
Multiple Inheritance
  • is a source of errors
  • results are hard to maintain
  • serves as obstacle to integration with
    neighboring ontologies
  • hampers formulation of coherent definitions
  • contravenes orthogonality
  • no coherently defined levels

31
Multiple Inheritance
  • can be easily dispensed with via normalization
    ???

32
DO
33
DO
34
OBO Relation Ontology
35
Three fundamental dichotomies
  • types vs. instances
  • continuants vs. occurrents
  • dependent vs. independent

36
Three fundamental dichotomies
  • types vs. instances
  • continuants vs. occurrents
  • dependent vs. independent

37
  • Glossary
  • Instance A particular entity in spatio-temporal
    reality.
  • Type A general kind instantiated by an
    open-ended totality of instances which share
    certain qualities and propensities in common of
    the sort that can be documented in scientific
    literature

38
Glossary
  • Biological process instance A change or complex
    of changes on the level of granularity of the
    cell or organism, mediated by one or more gene
    products.
  • Biological process type A type of biological
    process instance.

39
Glossary
  • Cellular component instance A part of a cell,
    including cellular structures, macromolecular
    complexes and spatial locations identified in
    relation to the cell
  • Cellular component type A type of cellular
    component.

40
Glossary
  • Molecular function instance The propensity of a
    gene product instance to perform actions, such as
    catalysis or binding, on the molecular level of
    granularity.
  • Molecular function type A type of molecular
    function instance (type of propensity)

41
SCIENCE TEXTS AREREPRESENTATIONS OF TYPES IN
REALITY of what is general in reality
42
  • CLINICAL GUIDELINES ARE REPRESENTATIONS OF TYPES
    IN REALITY
  • diseases, therapies, diagnostic procedures
    (measurements) are generals, with particular
    instances

43
ONTOLOGIES AREREPRESENTATIONS OF TYPES IN
REALITYaka kinds, universals, categories,
species, genera, ...
44
types
mammal
frog
45
two kinds of parthood
  • between instances
  • Marys heart part_of Mary
  • this nucleus part_of this cell
  • between types
  • human heart part_of human
  • cell nucleus part_of cell
  • Relations in Biomedical Ontologies, Genome
    Biology, Apr 2005

46
Three fundamental dichotomies
  • types vs. instances
  • continuants vs. occurrents
  • dependent vs. independent

47
  • Continuants (aka endurants)
  • have continuous existence in time
  • preserve their identity through change
  • exist in toto whenever they exist at all
  • Occurrents (aka processes)
  • have temporal parts
  • unfold themselves in successive phases
  • exist only in their phases

48
You are a continuant
  • Your life is an occurrent
  • You are 3-dimensional
  • Your life is 4-dimensional

49
Three fundamental dichotomies
  • types vs. instances
  • continuants vs. occurrents
  • dependent vs. independent

50
Dependent entities
  • require independent continuants as their bearers
  • There is no grin without a cat
  • There is no run without a runner
  • There is no pumping without a pump
  • There is no kiss without a kisser and a kissee

51
Dependent vs. independent continuants
  • Independent continuants (organisms, cells,
    molecules, environments)
  • Dependent continuants (qualities, shapes, roles,
    dispositions, propensities, functions)

52
All occurrents are dependent entities
  • They are dependent on those independent
    continuants which are their participants (agents,
    patients, media ...)

53
types
Continuant
Occurrent
Independent Continuant
Dependent Continuant
instances
54
Top-Level Ontology
Continuant
Occurrent (always dependent on one or more
independent continuants)
Independent Continuant
Dependent Continuant
types
instances
55
Top-Level Ontology
Continuant
Occurrent
Independent Continuant
Dependent Continuant
56
A representation of top-level types
Continuant
Occurrent
biological process
Independent Continuant
Dependent Continuant
cell component
molecular function
57
Continuant
Independent Continuant
anatomy
58
(No Transcript)
59
On Carcinomas and Other Pathological Entities,
Comparative and Functional Genomics, Apr. 2006
60
Top-Level Ontology
Continuant
Occurrent
Independent Continuant
Dependent Continuant
61
A representation of top-level types
Continuant
Occurrent
biological process
Independent Continuant
Dependent Continuant
cell component
molecular function
62
GOs three ontologies
occurrent
biological process
continuant
cellular component
molecular function
63
Functions, etc.Some dependent continuants are
realizable
  • expression of a gene
  • application of a therapy
  • realization of a protocol
  • execution of a function

64
The function of the heart is to pump blood
  • Not every activity (process) in an organism is
    the exercise of a function there are
  • mal functionings
  • side-effects (heart beating)
  • accidents (external interference)
  • background stochastic activity

65
The FMA is a canonical representation
  • It is a computational representation of types
    and relations between types deduced from the
    qualitative observations of the normal human body

66
The GO is a canonical representation
  • The Gene Ontology is a computational
    representation of the ways in which gene products
    normally function in the biological realm
  • Nucl. Acids Res. 2006 34.

67
GOs three ontologies
continuant
occurrent
cellular component
biological process
molecular function
68
GOs three ontologies
biological processes (including molecular
processes
biological functions at different levels of
granularity
biological continuants cellular components
FMA
69
Top-Level Ontology
Continuant
Occurrent
Independent Continuant
Dependent Continuant
Functioning
Side-Effect, Accident, Background Stochastic
Process, ...
Function
70
Disease vs. Event
  • Myocardial infarction is not a disease
  • A disease is something realizable
  • Disease ? Realization

71
Disease vs. Course of disease
  • Symptom-suppressant drugs demonstrate that a
    disease is not identical with any specific
    sequence or pattern of symptoms
  • Diseases are continuants that may exist even
    when their observable manifestations are not
    present

72
Top-Level Ontology
Continuant
Occurrent
Independent Continuant
Dependent Continuant
Functioning
Course or history of disease, mal- functionings
Disease
Function
73
Disease vs. symptom
  • Psoriasis as disease vs. psoriasis as
    manifestation (skin rash ...)
  • Cancer as disease vs. cancer as tumor

74
Disease vs. Bearer of disease
  • A mushy brain is not a disease
  • A broken leg is not a disease

75
types
Continuant
Occurrent
Independent Continuant
Dependent Continuant
Functioning
Side-Effect, Stochastic Process, ...
Function
Disease
instances
76
types
Continuant
Occurrent
Independent Continuant
Dependent Continuant
Functioning
Side-Effect, Stochastic Process, ...
Function
Disease
Marys pneumonia Marys
coughing
77
Functions are continuant instances
  • 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

78
Functions vs Functionings
  • the function of your heart to pump blood in
    your body
  • this function is realized in processes of
    pumping blood
  • not all functions are realized (consider the
    function of this sperm ...)
  • not all functions are realized normally

79
The Abnormality Theory of Disease
  • 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.
  • (Lawrie Reznek)
  • What are standard circumstances?
  • What are states and how do they issue in
    consequences?

80
"Defining Disease in the Genomics Era, Larissa
et al.
  • A disease is
  • a state that places individuals at increased risk
    of adverse consequences.
  • genetic variations with no adverse consequences
    (like Gilbert's syndrome) will be interesting but
    inconsequential polymorphisms

81
"Defining Disease in the Genomics Era, Larissa
et al.
  • A disease is
  • a state that places individuals at increased risk
    of adverse consequences.
  • Where is the threshold for adverse consequences
    (a) along the intensity dimension (b) along the
    time dimension?

82
  • A function is a disposition of a continuant to
    act in such a way as to contribute to the
    organisms survival
  • states issue in consequences continuants (e.g.
    cellular networks) have functions which are
    executed as patterns of functionings

83
The function of the kidney is to clean blood
84
Nephron
85
Functional Segments
86
Functions
functions based on shapes
87
Low hanging fruit
  • Why we should not just talk about conditions

88
What clinical medicine is for
  • to eliminate malfunctioning by fixing broken
    body parts
  • or to prevent the appearance of malfunctioning
    by intervening
  • or to alleviate the harmful consequences of this
    malfunctioning

89
molecular location
cellular location
organism-level location
90
organism-level physiology
cellular physiology
molecular process
normal (functionings)
molecular function (GO)
cell (types)
species
ChEBI, Sequence, RNA ...
cellular anatomy
anatomy (fly, fish, human...)
91
pathophysiology
pathological (malfunctionings)
pathoanatomy (fly, fish, human ...)
92
pathophysiology
disease
pathological (dispositional malfunctionings)
pathoanatomy (fly, fish, human ...)
93
Pathoanatomy
  • not disease of anatomical structure
  • but disease of pathonatomical structure
  • Types of pathoanatomical structures
  • malshapen limbs
  • pathological formations (tumors)
  • disturbed networks

94
  • Some pathoanatomical structures are not
    associated with a risk of adverse consequences
    (disorders)

95
Fiat vs. bona fide boundaries
96
Fiat vs. Bona Fide Boundaries
97
Colorado exists
98
Tumors exist
99
everything here is an independent continuant
100
structure vs. formation bona fide vs. fiat
boundaries
101
malgrowths
102
disease and anatomical damage
  • prokaryotic organisms do not have diseases
  • eukaryotic cells have a high number of different
    types of dispositions and form complex networks
    (such as the human brain) which can be damaged in
    ways which give rise to adverse effects

103
(Lou)
  • polio, ALS, myasthenia gravis, muscular
    distrophy begin with changes in the structures of
    certain cells (this we know)
  • if these changes lead to distortions in the
    network which compromise the viability of the
    organism, then the organism has a disease

104
Action item
  • Add molecular and cellular networks to the domain
    anatomy
  • Create a new discipline of network pathoanatomy
  • extend anatomy to networks
  • extend pathoanatomy to types of disturbed networks

105
pathoanatomy
  • There are malshaped networks and malshaped things
    (deformities)
  • and also genetic malmutations
  • which give rise to malfunctionings, behavioral
    abnormalities
  • The networks function
  • The malshaped network malfunctions

106
Boorse
  • Health is conformity to normal species design
    (as statistically determined).
  • (Biostatistical Theory)

107
Boorse
  • disease def. an impairment of normal functional
    ability
  • What Is Disease? J. M. Humber, R. F. Almeder,
    Eds., Humana Press, Totowa, NJ, 1997.

108
from Larissa, et al. Science 2001
  • To be considered a DISEASE, the genotypic or
    phenotypic state of the patient must have the
    potential for adverse consequences. In Gilbert's
    syndrome, there is an asymptomatic elevation of
    liver enzymes in response to stress, but this
    condition is not considered a DISEASE because it
    does not lead to adverse consequences. The World
    Health Organization's valuable classification of
    adverse consequences includes physical or
    psychological impairment, activity restrictions,
    and/or role limitations. The inclusion of role
    limitations is particularly important because it
    acknowledges the sociological consequences of
    DISEASE in terms of shortening the quantity of
    life or disturbing its quality. When determining
    states that are associated with DISEASE, the
    challenge is to describe potential adverse
    outcomes comprehensively and explicitly. Because
    an adverse consequence in one culture may not be
    viewed as such in another, this consideration
    must take into account different ethnic and
    cultural beliefs. For example, whereas menopause
    is considered a medical condition in North
    America, in other cultures it is viewed as a
    normal aspect of aging.

109
from Larissa, et al. Science 2001
  • The human genome sequence is likely to reveal
    many harmless genetic variations that will turn
    out not to be associated with DISEASE. Until we
    resolve questions about polymorphisms, incomplete
    penetrance of genetic mutations, and the
    contribution of environmental factors to DISEASE
    etiology, we will not be able to assess the
    probability of adverse consequences associated
    with a particular gene abnormality. There is
    little doubt that many genetic variations will
    have no consequences and, like those in
    individuals with Gilbert's syndrome, will be
    interesting but inconsequential polymorphisms.
    Until a mutation is shown to demonstrate a
    defined risk of developing adverse consequences,
    individuals carrying that mutation should not be
    considered DISEASEd. Defining adverse
    consequences and determining the risk of myriad
    small genetic variations is a mammoth task. But
    it is only with this information that clinicians
    can accurately define the term DISEASE in the
    genomics era, and in so doing, be able to advise
    their patients appropriately.

110
Enc Brit 1
  • an impairment of the normal state of an organism
    that interrupts or modifies its vital functions.
  • A brief discussion of disease follows. The
    subject is treated in a variety of articles. For
    a general discussion of human, animal, and plant
    diseases, see disease. For a discussion of
    diseases categorized according to their cause or
    transmission, see infection nutritional disease
    occupational disease. For a discussion of
    diseases associated with particular stages of
    human development, see childhood disease and
    disorder growth development. For a discussion
    of malignancy, which may affect any organ or
    tissue in the body, see cancer. For a discussion
    of disease-causing organisms such as viruses,
    bacteria, and parasites, see bacteria virus. For
    a discussion of bodily defenses against disease,
    see immune system. For a discussion of the
    diagnosis and treatment of disease, see
    diagnosis therapeutics drug medicine, history
    of. For a discussion of diseases affecting
    particular organs, tissues, or processes, see
    blood disease cardiovascular disease digestive
    system disease endocrine system, human renal
    system disease skin disease metabolic disease
    muscle disease nervous system disease
    reproductive system disease respiratory disease
    eye disease and ear disease connective tissue
    disease. For a discussion of neuroses and
    psychoses, see mental disorder. For a discussion
    of alcoholism and other drug addictions, see
    alcohol consumption.
  • Disease most commonly is caused by the invasion
    of an organism by one or more outside agents.
    Typically the infectious organisms are
    microorganisms (e.g., bacteria, viruses, and
    fungi), but they also can include larger
    organisms such as parasitic worms or nonliving
    but harmful substances such as toxins or ionizing
    radiation. Disease also may result from changes
    within the organisman anatomical fault
    (congenital or acquired) or a physiological
    malfunction (e.g., diabetes mellitus, in which
    the body fails to secrete or adequately utilize
    insulin, a hormone that regulates blood-sugar
    levels). Other diseases are a combination of
    external and internal factors. An organism's
    failure to adapt to changes in its environment
    can produce damaging changes within it.
    Physiological malfunctions and disturbances of
    normal growth can be induced by changes of diet
    or by invasion of microorganisms or other agents.
  • Nearly all organisms are able to defend
    themselves against most diseases. Humans and
    other vertebrates have developed two strategies
    of resistance, called immunity, to invading
    agents nonspecific immunity, which is present in
    all vertebrates at birth and specific immunity,
    which is acquired only after stimulation by the
    presence of a certain microbe or its products
    (e.g., the virus that causes chicken pox).
    Immunity also can be stimulated artificially in
    humans or other animals by inoculating them with
    microorganisms that have been killed (as in
    typhoid vaccine) or weakened (attenuated) ones
    (as in measles vaccine), which produce the
    defensive immune reaction without causing the
    disease.
  • Sometimes an organism's defensive reaction to
    invasion by an outside agent can become part of
    the disease. The crippling of the lungs produced
    by tuberculosis is caused partly by the
    destruction of lung tissue by the invading
    microorganism (in humans, usually Mycobacterium
    tuberculosis) and partly by the fibrous tissue
    that the body lays around the infection in a
    defensive reaction. Disorders of the immune
    response itself can produce autoimmune disease
    (e.g., rheumatoid arthritis) in which the immune
    response is triggered not by an outside invader
    but by the body's own tissues, which some cells
    fight against and try to reject. The immune
    system also can be disabled by an invading
    microorganism, as is the case with the disease
    AIDS.
  • Not all organisms that invade another produce
    disease. Some can establish a mutually beneficial
    relationship with their host without impairing
    its vital systems for example, the bacteria that
    live in the gastrointestinal tracts of humans and
    other vertebrates make possible the digestive
    processes of their hosts. In addition, organisms
    that are pathogenic to one species may be
    harmless to another.
  • A disease that becomes established in an organism
    usually requires some form of treatment. In most
    cases, treatment consists of administering drugs
    that kill the causative agent, restore any
    physiological or biochemical imbalances that have
    occurred, or control the symptoms caused by the
    agent so that the affected organism can continue
    to function. Other forms of treatment include
    moving the diseased organism to another
    environment or removing the diseased parts from
    the organism.
  • The most effective way to control disease is by
    preemptory prevention. The best method is to
    eliminate a disease-causing organism from the
    environment, such as by killing pathogens or
    parasites contaminating a water supply. Also
    effective is the disruption of a pathogen's
    transmission from one organism to another, either
    by avoiding contact with body tissues or fluids
    that harbour a pathogen or by eliminating an
    intermediary vector (e.g., killing the mosquitoes
    that transmit malaria to humans). Disease also
    may be prevented by removing a susceptible
    organism from an unhealthful environment,
    strengthening the organism's defenses by making
    it healthier, or vaccination.

111
everything here is an independent continuant
112
Functions are beneficial
  • those processes which are the realizations of a
    biological function Z are (in normal
    circumstances) beneficial to the organism
  • (? such as to sustain the organism in existence)

113
(No Transcript)
114
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

115
Prototypes
good functioning (sound anatomy)
116
Departures from Prototypes
reasonable functioning
117
Poor functioning
poor functioning
118
Malfunctioning
malfunctioning
119
Death?
not functioning at all
120
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

121
Disease remoteness from prototypical functioning
disease
122
(No Transcript)
123
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 instances Marys pneumonia

124
Need to take time into account
  • a forty year old man with rapidly dividing,
    highly invasive, cancerous prostate cells has the
    disease prostate cancer
  • a ninety year old man with slowly dividing
    cancerous prostate cells does not have the
    disease prostate cancer

125
  • A 90 year old man with Alzheimers probably had
    Alzheimers undiagnosed at the age of 40

126
The FMA is a canonical representation
  • but it recognizes also variant anatomical
    structures (e.g. coronary arteries or
    bronchopulmonary segments which deviate from the
    canonical anatomical pattern of organization)

127
canonical life Gestalten
  • variant life Gestalten (vegetarians)
  • pathological life Gestalten (serial murderers)

128
Model organisms
  • you can buy a mouse with the prototypical mouse
    Bauplan according to a precise specification

129
Just as there are 2 x n canonical Baupläne for
human beings (male and female at n successive
stages)
  • so there may be different canonical life plans
    for different types of human beings (in different
    types of contexts)
  • what are the different types?

130
What is a canonical environment?
  • What is a canonical family?

131
From Embryontology to Gerontology
  • Conception
  • Development
  • Birth
  • Infancy
  • Toddlerdom
  • Early Childhood
  • Childhood
  • Adolescence
  • Early Adulthood
  • Middle age
  • Old age
  • Death

132
What does every human canonical life involve?
  • 9 months of development (here the plan is very
    determinate)
  • birth
  • infancy
  • toddlerdom
  • later acquisition of consciousness, language
  • cycles of waking, sleeping eating and not eating
  • death

133
The organizing principle of complex living
systems
  • a life-like system def. any compact system
    containing an order and distribution of
    sustaining nonlinear limit cycle oscillators, and
    a related system of algorithmic guide mechanisms,
    that is capable of regulating its interior
    conditions for a considerable range of ambient
    environmental conditions so as to permit its own
    satisfactory preservative operation
  • Iberall, A. S. and McCulloch, W. S. The
    organizing principle of complex living systems.
    Journal of Basic Engineering. 290-294. June 1969.

134
Iberall and McCulloch
  • An essential characteristic of a living system
    is its marginal instability. Its principal
    dynamic properties are that it hungers, feeds,
    and can move or creep so that it can continue to
    hunger, feed, and move or creep.

135
Iberall and McCulloch 20 action modes
  • Action Modes of time
  • Sleeps 30
  • Eats 5
  • Drinks 1
  • Voids 1
  • Sexes 3
  • Works 25
  • Rests (no motor activity, indifferent internal
    sensory flux) 3
  • Talks 5
  • Attends (indifferent motor activity, involved
    sensory activity) 4
  • Motor practices (runs, walks, plays, etc.) 4
  • Angers 1
  • Escapes (negligible motor and sensory input) 1
  • Anxioius-es 2
  • Euphorics 2
  • Laughs 1
  • Aggresses 1
  • Fears, fights, flights 1
  • Interpersonally attends (body, verbal or sensory
    contact) 8

136
Functions
  • an entity has a biological function if and only
    if it is part of an organism and has a
    disposition to act reliably in such a way as to
    contribute to the organisms survival
  • doesnt apply to sperm
  • doesnt apply to carcinomatous lung

137
Revised formulation
  • an entity has a biological function if and only
    if it is part of an organism and has a
    disposition to act reliably in such a way as to
    contribute to the organisms realization of the
    canonical life plan for an organism of the
    relevant species

138
What clinical medicine is for
  • to bring the patient back in the direction of
    the canonical life for an organism of his stage
    of development
  • cure pulling you all the way back
  • life extension (can take you beyond the
    canonical life)

139
(No Transcript)
140
Disease (Some Hypotheses)
  • an anatomical structure in an organism has a
    certain function
  • this structure has become pathological
  • growths, pathogens, genetically determined
    deformations
  • and so malfunctions in ways which fall outside
    the species-typical range for an organism in this
    stage of development ( outside the canonical
    life)
  • and brings a high risk of adverse consequences

141
Disease remoteness from prototypical
functioning modulo stage of development and
environment
disease
142
A new proposed definition
  • X has a disease def.
  • X departs from the canonical life plan
    appropriate for Xs stage of development and
    environment
  • this departure brings (causally) risk of adverse
    consequences for X
  • this departure is rooted in an enduring
    pathoanatomical distortion

143
To apply this definition
  • we do not need to know the nature of the
    pathoanatomical distortion in every type of case

144
Implications for disease ontology
  • Focus on specific focal families of diseases
    where we can specify relevant pathoanatomical
    entities (including cellular networks ...) and
    relevant types of disturbances
  • A classification of diseases is a classification
    of those patterns of pathoanatomical disturbance
    which give rise to adverse consequences
  • Ignore the common cold ignore syndromes

145
Implications for disease ontology
  • Follow the principle of low-hanging fruit
  • Have these specifications created and validated
    by human experts
  • Take the structure and work with SNOMED for
    importing further content

146
United States
Colorado
147
Abnormality rooted in generalized pathoanatomy
disease
148
Abnormality rooted in generalized pathoanatomy
Enduring phenotypic abnormality
disease
149
DO
150
(No Transcript)
151
(No Transcript)
About PowerShow.com