Transcript The Future of Disease Ontology Barry Smith

The Future of Disease Ontology
Barry Smith
Department of Philosophy, University at Buffalo
National Center for Biomedical Ontology
http://ontology.buffalo.edu/smith
1
Colors form a continuum
2
colors form a
prototyped
continuum
3
strategy of
low hanging
fruit
focus on the
foci
(crosscultural,
lexicalized)
4
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
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A simple rule
Use singular nouns
Disease
Diseases
Disorder
Disorders
disorder
disease
disorders
diseases
6
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
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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
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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
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GO’s three ontologies
continuant
occurrent
biological
process
cellular
component
molecular
function
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RELATION
TO TIME
CONTINUANT
INDEPENDENT
OCCURRENT
DEPENDENT
GRANULARITY
ORGAN AND
ORGANISM
Organism
(NCBI
Taxonomy)
CELL AND
CELLULAR
COMPONENT
Cell
(CL)
MOLECULE
Anatomical
Organ
Entity
Function
(FMA,
(FMP, CPRO) Phenotypic
CARO)
Quality
(PaTO)
Cellular
Cellular
Component Function
(FMA, GO)
(GO)
Molecule
(ChEBI, SO,
RnaO, PrO)
Molecular Function
(GO)
Biological
Process
(GO)
Molecular Process
(GO)
Building out fron the original GO
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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.
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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.
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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
14
15
Goal: when we annotate diseaserelated 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
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Foundational Model of Anatomy
(FMA)
ontology of structural human anatomy
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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)
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Anatomical
Structure
Anatomical Space
Organ Cavity
Subdivision
Organ
Cavity
Organ
Serous Sac
Cavity
Subdivision
Serous Sac
Cavity
Serous Sac
Organ
Component
Organ
Subdivision
Pleural Sac
Pleural
Cavity
Parietal
Pleura
Interlobar
recess
Organ Part
Mediastinal
Pleura
Tissue
Pleura(Wall
of Sac)
Visceral
Pleura
Mesothelium
of Pleura
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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
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Example
Cell =Def. an anatomical structure which
consists of cytoplasm surrounded by a
plasma membrane
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at every level of granularity
22
The Gene Ontology
Cross-Species
Cross-Granularity
Impressive policies for maintenance
Has initiated logic-based reforms:
relations to other ontologies
relations among GO’s 3 ontologies
Aristotelian definitions
enhanced treatment of granularity
23
Multiple Inheritance
thing
car
blue thing
is_a
is_a
blue car
24
Multiple Inheritance
thing
blue thing
car
is_a1
is_a2
blue car
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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.
26
Multiple Inheritance
color
is_a
blue
thing
is_a
car
is_a
car #2947 is blue
dark blue
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Multiple Inheritance
anatomical structure
is_a
limb
fracture
is_a
spiral fracture
is_a
leg #29 has fracture #12
leg
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Multiple Inheritance
anatomical structure
is_a
heterogeneous
cluster
pharyngitis
is_a
infectious pharyngitis
is_a
pharynx
disease instance #12
inheres in pharynx #29
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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
30
Multiple Inheritance
can be easily dispensed with via
normalization ???
31
DO
32
DO
33
OBO Relation Ontology
34
Three fundamental dichotomies
• types vs. instances
• continuants vs. occurrents
• dependent vs. independent
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Three fundamental dichotomies
• types vs. instances
• continuants vs. occurrents
• dependent vs. independent
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Glossary
Instance: A particular entity in spatiotemporal 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
37
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.
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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.
39
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)
40
SCIENCE TEXTS ARE
REPRESENTATIONS OF
TYPES IN REALITY
= of what is general in reality
41
CLINICAL GUIDELINES ARE
REPRESENTATIONS OF TYPES
IN REALITY
diseases, therapies, diagnostic
procedures (measurements) are
generals, with particular instances
42
ONTOLOGIES ARE
REPRESENTATIONS OF
TYPES IN REALITY
aka kinds, universals,
categories, species, genera, ...
43
types
substance
organism
animal
mammal
cat
siamese
frog
instances
44
two kinds of parthood
1. between instances:
Mary’s heart part_of Mary
this nucleus part_of this cell
2. between types
human heart part_of human
cell nucleus part_of cell
“Relations in Biomedical Ontologies”, Genome
Biology, Apr 2005
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Three fundamental dichotomies
• types vs. instances
• continuants vs. occurrents
• dependent vs. independent
46
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
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You are a continuant
Your life is an occurrent
You are 3-dimensional
Your life is 4-dimensional
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Three fundamental dichotomies
• types vs. instances
• continuants vs. occurrents
• dependent vs. independent
49
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
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Dependent vs. independent
continuants
Independent continuants (organisms, cells,
molecules, environments)
Dependent continuants (qualities, shapes,
roles, dispositions, propensities, functions)
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All occurrents are dependent
entities
They are dependent on those independent
continuants which are their participants
(agents, patients, media ...)
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types
Continuant
Independent
Continuant
Occurrent
Dependent
Continuant
instances
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Top-Level Ontology
Continuant
Independent
Continuant
Occurrent
(always dependent
on one or more
independent
continuants)
Dependent
Continuant
types
instances
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Top-Level Ontology
Continuant
Independent
Continuant
Occurrent
Dependent
Continuant
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= A representation of top-level types
Continuant
Occurrent
biological process
Independent
Continuant
Dependent
Continuant
cell component
molecular function
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Continuant
Independent
Continuant
anatomy
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“On Carcinomas and Other Pathological Entities”,
Comparative and Functional Genomics, Apr. 2006
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Top-Level Ontology
Continuant
Independent
Continuant
Occurrent
Dependent
Continuant
60
= A representation of top-level types
Continuant
Occurrent
biological process
Independent
Continuant
Dependent
Continuant
cell component
molecular function
61
GO’s three ontologies
occurrent
continuant
cellular
component
biological
process
molecular
function
62
Functions, etc.
Some dependent continuants are
realizable
expression of a gene
application of a therapy
realization of a protocol
execution of a function
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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
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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
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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.
66
GO’s three ontologies
continuant
cellular
component
molecular
function
occurrent
biological
process
67
GO’s
+
three
ontologies
biological
processes
(including
molecular
processes
biological
functions at
different levels of
granularity
biological
continuants =
cellular
components +
FMA
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Top-Level Ontology
Continuant
Independent
Continuant
Dependent
Continuant
Function
Occurrent
Functioning
Side-Effect,
Accident,
Background
Stochastic
Process,
...
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Disease vs. Event
Myocardial infarction is not a disease
A disease is something realizable
Disease ≠ Realization
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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
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Top-Level Ontology
Continuant
Independent
Continuant
Occurrent
Dependent
Continuant
Function
Functioning
Disease
Course or
history
of disease,
malfunctionings
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Disease vs. symptom
Psoriasis as disease vs. psoriasis as
manifestation (skin rash ...)
Cancer as disease vs. cancer as tumor
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Disease vs. Bearer of disease
A mushy brain is not a disease
A broken leg is not a disease
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types
Continuant
Independent
Continuant
Function
Occurrent
Dependent
Continuant
Functioning
Side-Effect,
Stochastic
Process, ...
Disease
instances
75
types
Continuant
Independent
Continuant
Function
Dependent
Continuant
Occurrent
Functioning
Side-Effect,
Stochastic
Process, ...
Disease
Mary’s pneumonia
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Mary’s coughing
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
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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
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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 circumstances;
something 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?
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"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
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"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?
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A function is a disposition of a continuant
to act in such a way as to contribute to
the organism’s survival
states issue in consequences =
continuants (e.g. cellular networks) have
functions which are executed as patterns
of functionings
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The function of the kidney is to clean
blood
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Nephron
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Functional Segments
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Functions
functions based on shapes
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Low hanging fruit
Why we should not just talk about conditions
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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
88
molecular
process
cellular
process
organismlevel
process
functionings
functionings
functionings
cellular
function
organismlevel
biological
function
molecule
cellular
component
organism
molecular
location
cellular
location
organismlevel
location
molecular
function
89
molecula
r process
cellular
physiology
organism-level
physiology
molecula
r function
(GO)
normal
(functionings)
cell
(types)
species
cellular
anatomy
anatomy
(fly, fish,
human...)
ChEBI,
Sequence,
RNA ...
90
pathophysiology
pathological
(malfunctionings)
pathoanatomy
(fly, fish, human ...)
91
disease
pathophysiology
pathological
(dispositional
malfunctionings)
pathoanatomy
(fly, fish, human ...)
92
Pathoanatomy
not: disease of anatomical structure
but: disease of pathonatomical structure
Types of pathoanatomical structures:
malshapen limbs
pathological formations (tumors)
disturbed networks
93
Some pathoanatomical structures are not
associated with a risk of adverse
consequences (‘disorders’)
94
Fiat vs. bona fide boundaries
95
Fiat vs. Bona Fide Boundaries
Fiat boundary
Physical boundary
96
Colorado exists
97
Tumors exist
98
everything here is an
independent continuant
99
structure vs. formation =
bona fide vs. fiat
boundaries
100
malgrowths
101
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
102
(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
103
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
104
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
105
Boorse
Health is conformity to normal species
design (as statistically determined).
(Biostatistical Theory)
106
Boorse
disease =def. an impairment of normal
functional ability
What Is Disease? J. M. Humber, R. F. Almeder, Eds.,
Humana Press, Totowa, NJ, 1997.
107
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.
108
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.
109
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 organism—an 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.
110
everything here is an
independent continuant
111
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)
112
113
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
114
Prototypes
good
functioning
(sound
anatomy)
115
Departures from Prototypes
reasonable
functioning
116
Poor functioning
poor
functioning
117
Malfunctioning
malfunctioning
118
Death?
not
functioning
at all
119
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
120
Disease = remoteness from
prototypical functioning
disease
121
122
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 = Mary’s pneumonia
123
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
124
A 90 year old man with Alzheimers probably
had Alzheimers undiagnosed at the age of
40
125
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)
126
canonical life Gestalten
+ variant life Gestalten (vegetarians)
+ pathological life Gestalten (serial murderers)
127
Model organisms
you can buy a mouse with the prototypical
mouse Bauplan according to a precise
specification
128
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?
129
What is a canonical environment?
What is a canonical family?
130
From Embryontology to
Gerontology
Conception
Development
Birth
Infancy
Toddlerdom
Early Childhood
Childhood
Adolescence
Early Adulthood
Middle age
Old age
Death
131
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
132
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.
133
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.
134
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
Envies
1
Greeds
1
Total:
100% +/- 20% of time involvement
135
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 organism’s survival
doesn’t apply to sperm
doesn’t apply to carcinomatous lung
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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 organism’s
realization of the canonical life plan for
an organism of the relevant species
137
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)
138
139
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
140
Disease = remoteness from
prototypical functioning modulo stage
of development and environment
disease
141
A new proposed definition
X has a disease =def.
i. X departs from the canonical life plan
appropriate for X‘s stage of development
and environment
ii. this departure brings (causally) risk of
adverse consequences for X
iii. this departure is rooted in an enduring
pathoanatomical distortion
142
To apply this definition
we do not need to know the nature of the
pathoanatomical distortion in every type of
case
143
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
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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
145
United States
Colorado
146
Abnormality rooted in generalized
pathoanatomy
disease
147
Enduring phenotypic abnormality
Abnormality rooted in generalized
pathoanatomy
disease
148
DO
149
150
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