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R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Academic Development Symposium
Foundations for a
Realist Ontology of Mental Disease
August 25, 2010; 11.30 AM - 01.00 PM
ECMC – Department of Psychiatry, Buffalo NY
Room 1108A
Werner CEUSTERS1 and Barry SMITH2
1,2 Ontology
Research Group, Center of Excellence in Bioinformatics and Life Sciences
1 Department of Psychiatry, University at Buffalo, NY, USA
2 Department of Philosophy, University at Buffalo, NY, USA
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Structure of this presentation
1. Do mental disorders exist and if so, what are
they?
– Overview of relevant positions
2. Foundations of our work
– Methodological
– Representational
3. Towards an ontology for mental health
4. Utility of our work
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Center of Excellence in
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Mental disorders
and
‘mental disorders’
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Center of Excellence in
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What is a mental disorder ?
• The social-constructivist position:
– mental disorder is a value-laden social construct with no
counterpart in biomedical reality.
• The objectivist position:
– mental disorders are natural entities that could be understood in
biological terms.
• The hybrid position:
– Mental disorder is harmful dysfunction.
• the social definition of "harm" is counterbalanced by a factual component
of a malfunctioning internal mechanism causing objective dysfunction.
Jablensky A: Does psychiatry need an overarching concept of "mental disorder"? World Psychiatry 2007, 6:157-158.
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Center of Excellence in
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A terminological and ontological problem (1)
• WHO: Lexicon of psychiatric and mental health
terms. Second edn. Geneva: WHO; 1994.
– ‘mental disorder: an imprecise term designating any disorder of
the mind, acquired or congenital’
– ‘organic mental disorder: a range of mental disorders grouped
together on the basis of their having in common a demonstrable
etiology in cerebral disease, brain injury, or other insult,
leading to cerebral dysfunction’.
• Does WHO rule out the existence of mental
disorders which are not due to brain disorder?
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Center of Excellence in
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A terminological and ontological problem (2)
• Szasz: ‘mental illness is a myth whose function it
is to disguise and thus render more palatable the
bitter pill of moral conflicts in human relations’
– Szasz TS: The Myth of Mental Illness. American Psychologist
1960, 15:113-118.
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Center of Excellence in
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Our interpretation of Szasz (1)
• the group of persons ‘known to manifest various
peculiarities or disorders of thinking and behavior’ and
about which it is therefore said that they have a mental
illness, consists of two subgroups:
– (1) those for which there is an underlying brain
disorder perhaps not yet discoverable by what the state
of the art is able to offer; and
– (2) those who exhibit in their behavior a ‘deviance …
from certain psychosocial, ethical, or legal norms’ as
judged by themselves, by clinicians, or by others.
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Center of Excellence in
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Our interpretation of Szasz (2)
• Those in group (1), according to Szasz, would be
better described as having a brain disorder,
• those in group (2), while they might indeed have
‘problems of living’, and thus be suffering, are not
suffering because of some disorder of a special,
mental kind.
– Szasz hereby rejects as fallacious the view which regards social
intercourse ‘as something inherently harmonious, its
disturbance being due solely to the presence of “mental illness”
in many people’.
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A terminological and ontological problem (3)
• Adoption of a generic, presumably universal,
definition of "mental disorder" would be
premature. It may cause more harm than good to
psychiatry.
– Jablensky A: Does psychiatry need an overarching
concept of "mental disorder"? World Psychiatry
2007, 6:157-158.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Jablensky’s arguments (1)
• A terminological argument
– Neither disease nor health has ever been strictly and
unambiguously defined in terms of finite sets of observable
referential phenomena.
• Arguments of utility:
– the medical person is least concerned with what healthy and
sick mean in general ... we do not need the concept of ‘illness in
general’ at all
• Jaspers K. General psychopathology. Birmingham: Birmingham University Press; 1963.
– doctors do not concern themselves with maximizing the
evolutionary advantages of the human race as a whole, but with
aiding individuals
• Toon PD. Defining "disease" - classification must be distinguished from evaluation. J Med Ethics.
1981;7:197–201.
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Center of Excellence in
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Jablensky’s arguments (2)
• Ontological argument:
– we now know that no such general and uniform concept exists.
• Jaspers K. General psychopathology ,Birmingham: Birmingham University Press; 1963..
• Epistemological argument:
– the emergence of molecular genetic classifications of large
groups of diseases, and the concomitant availability of genetic
diagnostic tests, raise the possibility that the entire taxonomy of
human disease may eventually be revised.
• We believe these arguments are flawed and do not
lead to the conclusion
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Center of Excellence in
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Missing the nail
• A definition of ‘mental disorder’ should be such (a) that it
‘can be used as a criterion for assessing potential
candidates for inclusion in the classification, and
deletions from it’ and (b) that there should be ‘at least no
ambiguity about the reason that individual candidate
diagnoses are included or excluded’.
–
Kupfer D, First M, Regier D (Eds.): A Research Agenda for DSM-V, American Psychiatric Association;
2002.
• This doesn’t address at all what candidate mental
disorders have in common, i.e. what differentiates them
from other, non-mental disorders.
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ICD-10 Mental disease guidelines
• Two distinct ones:
– The ICD-10 Classification of Mental and Behavioural
Disorders: Clinical descriptions and diagnostic
guidelines. Geneva: World Health Organization; 1992.
– The ICD-10 Classification of Mental and Behavioural
Disorders: Diagnostic criteria for research. Geneva:
World Health Organization; 1993.
• Yet, an individual entity, such as a mental disorder
in a specific patient, does not change when looked
at from distinct perspectives.
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Goal of mental disease guidelines
• Goal: to reduce the variability in coding caused by
two sorts of disagreement which can arise when
diagnoses are being made:
– differences in opinion amongst clinicians about what type of
mental disorder a patient with a certain configuration of
symptoms and test results is suffering from;
• in this case the disagreement is about the diagnosis independent of the
diagnostic options offered by the ICD or DSM;
– differences in opinion about what ICD or DSM classification
code should be used in case there is agreement about a
diagnosis.
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Pies’ model
• Introduces a 5-stage account of how our scientific
understanding of a mental disease condition might
evolve over time. The goal is a framework that is
designed to allow us to determine:
whether a condition represents, in the first place, dis-ease and,
secondarily, whether it constitutes a specific disease, on a par with,
say, bipolar I disorder.
For example, how do we decide whether to consider “pathological
bigotry” and “internet addiction” as specific mental disorders?
Pies R: What should count as a mental disorder in DSM-V. Psychiatric Times 2009, 26.
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The basics: existence (in a patient) criterion
• ‘prolonged and severe suffering and incapacity in
the affective, cognitive, or interpersonalbehavioral realms’
– Pies R: What should count as a mental disorder in DSM-V.
Psychiatric Times 2009, 26.
• based on:
– Kendell RE: The concept of disease and its implications for
psychiatry. British Journal of Psychiatry 1975, 127:305-315.
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Pies’ 5-stage model (1)
• Stage 1: patient’s acknowledgement of daily
substantial and prolonged suffering and
incapacity that is ‘specified in terms of social and
vocational impairment, impaired vital functions,
and distortions in the phenomenological realm
(feeling “totally worthless,” “like I’m nothing”)’.
– This must be acknowledged as an intrinsic element of
the condition and not simply as a consequence of
society’s punitive responses to the person’s behavior.
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Pies’ 5-stage model (2)
• Stage 2:
– availability of a general syndromal description of the
condition supported by evidence that the constituent
signs and symptoms reliably ‘hang together’ over long
periods and in geographically distant populations.
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Pies’ 5-stage model (3)
• Stage 3:
– the syndrome has been characterized by authoritive
sources in terms of usual course, outcome,
comorbidity, familial pattern, and response to
treatment;
– there may also be preliminary data on pathophysiology
and biomarkers, and a more specific understanding of
the afflicted person’s phenomenology
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Center of Excellence in
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Pies’ 5-stage model (4)
• Stage 4:
– known pathophysiology, cause, a specific set of
biomarkers, and
– in some cases an inheritance pattern for the condition
(or for multiple conditions that become identified as
separate entities only after Stage 2).
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Center of Excellence in
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Pies’ 5-stage model (5)
• Stage 5:
– availability of a precise chromosomal and biomolecular
etiology, and
– a specification of the phenomenology, for all disease
subtypes.
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Center of Excellence in
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Foundations for an
Ontology of Mental Health
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Foundations for our work
• Methodological foundations:
– Ontological Realism
– Open Biomedical Ontologies Foundry
• Representational foundations:
– Basic Formal Ontology
– Relation Ontology
– Ontology of General Medical Science
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Center of Excellence in
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Ontology
• In philosophy:
– Ontology (no plural) is the study of what entities exist and how they
relate to each other;
• In computer science and many biomedical informatics
applications:
– An ontology (plural: ontologies) is a shared and agreed upon
conceptualization of a domain;
• The realist view within the Ontology Research Group
combines the two:
– We use realism, a specific theory of ontology, as the basis for
building high quality ontologies, using reality as benchmark.
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Center of Excellence in
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Ontological realism
1. There is an external reality which
is ‘objectively’ the way it is;
2. That reality is accessible to us;
3. We build in our brains cognitive
representations of reality;
4. We communicate with others
about what is there, and what we
believe there is there.
Smith B, Kusnierczyk W, Schober D, Ceusters W. Towards a Reference Terminology for Ontology Research and Development in the
Biomedical Domain. Proceedings of KR-MED 2006, Biomedical Ontology in Action, November 8, 2006, Baltimore MD, USA
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Center of Excellence in
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Realism versus other philosophies
Realism
Conceptualism Nominalism
• Basic questions:
– What does a
general term
such as
‘disorder’ refer
to?
Universal
Concept
Collection
of
particulars
– Do generic
things exist?
yes: in
particulars
perhaps: in
minds
no
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Center of Excellence in
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Three
Terminology
levels of reality in Ontological
Realist Ontology
Realism
Representation and Reference
representational units
(3) Representational units in various
forms about (1), (2) or (3)
cognitive
units
communicative
units
universals
particulars
(2) Cognitive entities which are our
beliefs about (1)
(1) Entities with objective existence
which are not about anything
First Order Reality
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Center of Excellence in
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Basic Formal Ontology
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Center of Excellence in
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Basic Formal Ontology in a nutshell
• The world consists of
– entities that are
• Either particulars or universals;
• Either occurrents or continuants;
• Either dependent or independent;
and,
– relationships between these entities of the form
• <particular , universal>
• <particular , particular>
• <universal , universal>
e.g. is-instance-of,
e.g. is-member-of
e.g. isa (is-subtype-of)
Smith B, Kusnierczyk W, Schober D, Ceusters W. Towards a Reference Terminology for Ontology Research and
Development in the Biomedical Domain. Proceedings of KR-MED 2006, November 8, 2006, Baltimore MD, USA
R T U New York State
Center of Excellence in
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1
Particulars and Universals
process
living creature
function
leg
human being
Instance-of
at t
Instance-of
at t
Instance-of
at t
leg moving
walking
Instance-of
to make
me walk
this leg moving
Instance-of
my left leg
me
this walking
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Center of Excellence in
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The importance of temporal indexing
malignant
tumor
benign
tumor
instanceOf at t1
instanceOf at t2
partOf at t1
this-4
partOf at t2
stomach
instanceOf at t2
instanceOf at t1
this-1’s stomach
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Center of Excellence in
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2
Continuants and Occurrents
process
living creature
function
leg
human being
Instance-of
at t
Instance-of
at t
Instance-of
at t
leg moving
walking
Instance-of
to make
me walk
this leg moving
Instance-of
my left leg
me
this walking
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Center of Excellence in
Bioinformatics & Life Sciences
3
Independent versus dependent
Independent entities
Do not require any
other entity to exist
for their own
existence
Independent
continuants
my left leg
me
Dependent entities
Require the existence
of some other entity
for their existence
to make
me walk
Dependent
continuants
this leg moving
Occurrents
(are all dependent)
this walking
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3
Dependent continuants
continuants
occurrents
• Realized
– Quality:
redness (of blood)
• Realizable
–
–
–
–
Function:
Role:
Power:
Disposition:
Realizations
to flex (of knee joint)
student
boss
brittleness (of a bone)
flexing
studying
ordering
breaking
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Disposition
• A disposition is a realizable entity which is such
that
(1) if it ceases to exist, then its bearer is physically
changed,
(2) whose realization occurs, in virtue of the
bearer’s physical make-up, when this bearer is in
some special physical circumstances
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Center of Excellence in
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Relation Ontology
universals
has_participant
Continuant
isa
isa
Independent
Continuant
Dependent
Continuant
Occurrent
process, event
~ thing
.... ..... .......
inheres_in
particulars
instance_of (at t)
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Center of Excellence in
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The essential pieces
dependent
continuant
material
object
t
history
me
… at t
spatial
region
instanceOf
t
participantOf at t
some
quality
spacetime
region
t
occupies
my
life
my 4D
STR
projectsOn at t
located-in at t
some
spatial
region
temporal
region
projectsOn
some
temporal
region
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Center of Excellence in
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The OBO Foundry
• a family of interoperable biomedical reference
ontologies built around the Gene Ontology (GO)
at its core and using the same principles as the GO
• a modular annotation catalogue of English phrases
• each module created by experts from the
corresponding scientific community
• http://obofoundry.org
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OBO Website
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OBO Foundry ontologies in BFO-dress
RELATION
TO TIME
GRANULARITY
CONTINUANT
INDEPENDENT
ORGAN AND
ORGANISM
Organism
(NCBI
Taxonomy)
CELL AND
CELLULAR
COMPONENT
Cell
(CL)
MOLECULE
DEPENDENT
Anatomical
Organ
Entity
Function
(FMA,
(FMP, CPRO) Phenotypic
CARO)
Quality
(PaTO)
Cellular
Cellular
Component Function
(FMA, GO)
(GO)
Molecule
(ChEBI, SO,
RnaO, PrO)
OCCURRENT
Molecular Function
(GO)
Biological
Process
(GO)
Molecular Process
(GO)
41
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Ontology of General Medical Science
First ontology in which the
L1/L2/L3 distinction is used
Scheuermann R, Ceusters W, Smith B. Toward an Ontological Treatment of Disease and Diagnosis. 2009
AMIA Summit on Translational Bioinformatics, San Francisco, California, March 15-17, 2009;: 116-120.
Omnipress ISBN:0-9647743-7-2
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Goal of OGMS
• To be a consistent, logical and extensible
framework (ontology) for the representation
of
– features of disease
– clinical processes
– results
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Motivation
• Clarity about:
– disease etiology and progression
– disease and the diagnostic process
– phenotype and signs/symptoms
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Big Picture
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Approach
• a disease is a disposition rooted in a physical disorder in the
organism and realized in pathological processes.
produces
etiological process
bears
disorder
realized_in
disposition
pathological process
produces
diagnosis
interpretive process
produces
signs & symptoms
participates_in
abnormal bodily features
recognized_as
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Center of Excellence in
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Cirrhosis - environmental exposure
•
•
•
•
•
•
•
Etiological process - phenobarbitolinduced hepatic cell death
– produces
Disorder - necrotic liver
– bears
Disposition (disease) - cirrhosis
– realized_in
Pathological process - abnormal tissue
repair with cell proliferation and
fibrosis that exceed a certain
threshold; hypoxia-induced cell death
– produces
Abnormal bodily features
– recognized_as
Symptoms - fatigue, anorexia
Signs - jaundice, splenomegaly
•
•
•
•
•
•
•
Symptoms & Signs
– used_in
Interpretive process
– produces
Hypothesis - rule out cirrhosis
– suggests
Laboratory tests
– produces
Test results – documentation of
elevated liver enzymes in serum
– used_in
Interpretive process
– produces
Result - diagnosis that patient X has a
disorder that bears the disease
cirrhosis
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Influenza - infectious
•
•
•
•
•
•
•
Etiological process - infection of
airway epithelial cells with influenza
virus
– produces
Disorder - viable cells with influenza
virus
– bears
Disposition (disease) - flu
– realized_in
Pathological process - acute
inflammation
– produces
Abnormal bodily features
– recognized_as
Symptoms - weakness, dizziness
Signs - fever
•
Symptoms & Signs
– used_in
• Interpretive process
– produces
• Hypothesis - rule out influenza
– suggests
• Laboratory tests
– produces
• Test results – documentation of elevated
serum antibody titers
– used_in
• Interpretive process
– produces
• Result - diagnosis that patient X has a
disorder that bears the disease flu
But the disorder also induces normal
physiological processes (immune response)
that can result in the elimination of the
disorder (transient disease course).
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Foundational Terms (1)
• Disorder =def. – A causally linked combination of
physical components that is
– (a) clinically abnormal and
– (b) maximal, in the sense that it is not a part of some larger such
combination.
• Pathological Process =def. – A bodily process that is a
manifestation of a disorder and is clinically abnormal.
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Clinically abnormal
• - something is clinically abnormal if:
– (1) is not part of the life plan for an organism of the
relevant type (unlike aging or pregnancy),
– (2) is causally linked to an elevated risk either of pain
or other feelings of illness, or of death or dysfunction,
and
– (3) is such that the elevated risk exceeds a certain
threshold level.
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Foundational Terms (2)
• Disorder =def. – A causally linked combination of
physical components that is (a) clinically abnormal and
(b) maximal, in the sense that it is not a part of some
larger such combination.
• Pathological Process =def. – A bodily process that is a
manifestation of a disorder and is clinically abnormal.
• Disease =def. – A disposition (i) to undergo pathological
processes that (ii) exists in an organism because of one or
more disorders in that organism.
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Diagnosis
• Clinical Picture =def. – A representation of a
clinical phenotype that is inferred from the
combination of laboratory, image and clinical
findings about a given patient.
• Diagnosis =def. – A conclusion of an interpretive
process that has as input a clinical picture of a
given patient and as output an assertion to the
effect that the patient has a disease of such and
such a type.
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Some motivations and consequences (2)
• A diagnosis can be of level 2 or level 3, i.e. either
in the mind of a cognitive agent, or in some
physical form.
• Allows for a clean interpretation of assertions of
the sort ‘these patients have the same diagnosis’:
 The configuration of representational units is such
that the parts which do not refer to the particulars
related to the respective patients, refer to the same
portion of reality.
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Ontology for Mental Health
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Ontology for Mental Health V0.0001
Legend
continuant
representation
process
disjunction
MHO
BFO/OGMS
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MENTAL PROCESS (L1,U)
• =def.
BODILY PROCESS which brings into being,
sustains or modifies a COGNITIVE
REPRESENTATION or a BEHAVIOR INDUCING
STATE
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BEHAVIOR INDUCING STATE (L1,U)
• =def.
BODILY QUALITY inhering in a MENTAL
FUNCTIONING RELATED ANATOMICAL
STRUCTURE which leads to BEHAVIOR of some
specific sort
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BEHAVIOR (L1,U)
• =def.
a PROCESS having PROCESSES as parts in which
an ORGANISM participates as agent in response to
external or internal stimuli and following some
pattern which is dependent upon some
combination of that ORGANISM’s internal state
and external conditions. (Derived from the Gene
Ontology)
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MENTAL FUNCTIONING RELATED ANATOMICAL
STRUCTURE (L1,U)
• =def.
ANATOMICAL STRUCTURE in which there inheres
the DISPOSITION to be the agent of a MENTAL
PROCESS
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Disorder related definitions
• MENTAL DISORDER (L1,U) =def. DISORDER in a
MENTAL FUNCTIONING RELATED ANATOMICAL
STRUCTURE
• PATHOLOGICAL MENTAL PROCESS (L1,U) =def.
PATHOLOGICAL PROCESS which is the manifestation of
a MENTAL DISORDER
• MENTAL DISEASE (L1,U) =def. a DISEASE which is a
DISPOSITION to undergo PATHOLOGICAL MENTAL
PROCESSES
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Diagnosis related entities (skip)
• DIAGNOSIS OF MENTAL DISEASE (L2/L3,U) =def. DIAGNOSIS asserting
the presence of an instance of MENTAL DISEASE in a given ORGANISM
• DISEASE PICTURE (L3, CLS) =def. REPRESENTATION of a DISEASE
PHENOTYPE
• DISEASE PICTURE COMPONENT (L3, CLS) =def. REPRESENTATIONAL
UNIT which either (1) represents (or is believed to represent) a BODILY
FEATURE that is believed to be manifested in the DISEASE PHENOTYPE
represented by the DISEASE PICTURE of which this REPRESENTATIONAL
UNIT is a component or (2) expresses a negative finding
• MARKER FEATURES FOR DISEASE X (L3, CLS) =def.
REPRESENTATION which is a collection of DISEASE PICTURE
COMPONENTS which are characteristic for DISEASE X (where ‘X’ serves
as placeholder for some disease name)
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Future work: a template like this for each mental disease
•
•
•
•
•
•
•
Etiological process - phenobarbitolinduced hepatic cell death
– produces
Disorder - necrotic liver
– bears
Disposition (disease) - cirrhosis
– realized_in
Pathological process - abnormal tissue
repair with cell proliferation and
fibrosis that exceed a certain
threshold; hypoxia-induced cell death
– produces
Abnormal bodily features
– recognized_as
Symptoms - fatigue, anorexia
Signs - jaundice, splenomegaly
•
•
•
•
•
•
•
Symptoms & Signs
– used_in
Interpretive process
– produces
Hypothesis - rule out cirrhosis
– suggests
Laboratory tests
– produces
Test results – documentation of
elevated liver enzymes in serum
– used_in
Interpretive process
– produces
Result - diagnosis that patient X has a
disorder that bears the disease
cirrhosis
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Use in study design and data collection
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Typical approach (1)
• Building a huge matrix with patient cases in one dimension
and patient characteristics in the other dimension
Characteristics
Cases
ch1
case1
case2
case3
case4
case5
case6
...
ch2
ch3
ch4
ch5
ch6
...
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Typical approach (2)
• Use statistical correlation techniques to find associations
between characteristics and (dis)similarities between cases
Characteristics
Cases
ch1
case1
case2
case3
case4
case5
case6
...
ch2
ch3
ch4
ch5
ch6
...
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Fundamental questions
1.
2.
What is a characteristic ?
What (sorts of) characteristics (relevant for psychiatry) go in here ?
Characteristics
Cases
ch1
ch2
ch3
ch4
ch5
ch6
...
case1
case2
case3
case4
case5
case6
...
3.
4.
5.
How can we make distinct studies comparable?
Because such matrices tend to become huge, how can we make analysis feasible ?
How can we make results re-usable?
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Q1: what is a characteristic ?
– it is for sure not a category entities can belong to: there
is no natural class of entity for which the name
‘characteristic’ would be appropriate;
– there is also no particular entity that you could point to
and state ‘that over there is the only existing
characteristic’
– thus: there are no characteristics, there is just the term
‘characteristic’ which is used to describe that some
entities are (acknowledged to be) in some way of
interest in some context and for some purpose.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
This requires rephrasing Q2
What (sorts of) characteristics (relevant for
psychiatry) go in here?
What entities described as being characteristic for
psychiatric purposes should be represented here?
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Examples
Universals
• portion of C17H19ClN2S.HCl
Independent • human being
Continuant • gene
Continuant
Dependent
Continuant
Particulars
• portion of chlorpromazine in this tablet
• me
• the HTR2A gene on chromosome 13 of the
most frontal cell in the tip of my nose
• shape
• the shape of my nose
• temperature
• the temperature of the chlorpromazine tablet in
front of me
• length
• the length of that HTR21 gene
• change in shape
• unfolding of a DNA molecule
• motion
• the circulation of a chlorpromazine molecule in
my bloodstream
• rise in temperature
• the rise of my body temperature while teaching
this seminar
Occurrent
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Q3: How can we make distinct studies comparable?
• Map any characteristic used to relevant, standard
and high quality ontologies
Characteristics
Cases
ch1
case1
case2
case3
case4
case5
case6
...
ch2
ch3
ch4
ch5
ch6
...
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
The positive effects of appropriate mappings
Characteristics
Cases
ch1
ch2
ch3
ch4
ch5
ch6
...
ch6
...
case1
case2
case3
case4
case5
case6
...
Characteristics
Cases
ch1
ch2
ch3
ch4
ch5
Characteristics
Cases
ch6
...
ch1
case1
case1
case2
case2
case3
case3
case4
case4
case5
case5
case6
case6
...
...
ch2
ch3
ch4
ch5
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
The positive effects of appropriate mappings
Characteristics
Cases
ch1 ch2 ch3 ch4 ch5 ch6 ...
case1
case2
–
–
–
–
case3
case4
case5
case6
...
Characteristics
Cases
ch1
ch2
ch3
ch4
ch5
Characteristics
Cases
ch6 ...
ch1
case1
case1
case2
case2
case3
case3
case4
case4
case5
case5
case6
case6
...
...
• identification of ontological
relations prior to statistical
correlation:
ch2
ch3
ch4
ch5
ch6 ...
ch1 and ch4
ch1 and ch5
ch1 and ch2
…
• Contributes to answering
‘Q4: how can we make
analysis feasible’
– this method allows for datareduction without information
loss.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Filling the grid
• We know now that labels from appropriate
ontologies go here
Characteristics
Cases
ch1
case1
case2
case3
case4
case5
case6
...
• But, what goes here?
ch2
ch3
ch4
ch5
ch6
...
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Remember we had this …
Universals
• portion of C17H19ClN2S.HCl
Independent • human being
Continuant • gene
Continuant
Dependent
Continuant
Particulars
• portion of chlorpromazine in this tablet
• me
• the HTR2A gene on chromosome 13 of the
most frontal cell in the tip of my nose
• shape
• the shape of my nose
• temperature
• the temperature of the chlorpromazine tablet in
front of me
• length
• the length of that HTR21 gene
• change in shape
• unfolding of a DNA molecule
• motion
• the circulation of a chlorpromazine molecule in
my bloodstream
• rise in temperature
• the rise of my body temperature while talking
here
Occurrent
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Or after transposition …
Universals
Continuant
Independent
Continuant
portion of
C17H19ClN2
S.HCl
human
being
Occurrent
Dependent
Continuant
gene
shape
temperature
length
change
in shape
motion
rise in temperature
Particulars
• portion of chlorpromazine in
the tablet in front of me
• me
• the HTR2A gene on
chromosome 13 of the most
frontal cell in the tip of my
nose
• the shape of my nose
• unfolding of a DNA molecule
• the temperature of the
chlorpromazine tablet in
front of me
• the circulation of a chlorpromazine molecule in
my bloodstream
• the length of that HTR21
gene
• the rise of my body temperature while teaching
this seminar
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
… and for many patients
Universals
Continuant
Independent
Continuant
portion of
C17H19ClN2S. HCl
case1
Particulars
case2
.
case3
case4
case5
case6
case7
case8
…
.
human
being
..
..
..
.
Occurrent
Dependent
Continuant
gene
shape
..
.
..
temperature
length
change
in shape
motion
. . .
.
.
.
.. .
..
.
.
.
rise in temperature
.
..
..
.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Referent Tracking
Universals
Continuant
Independent
Continuant
portion of
human gene shape temperature
C19H17ClN2O4 being
case1
Particulars
case2
case3
case4
case5
case6
case7
case8
…
. ..
..
. ..
.
Occurrent
Dependent
Continuant
..
.
..
length
change
in shape
motion
. . .
.
.
.
.. . ..
.
.
.
rise in temperature
.
..
..
.
unique
identification
by means of
‘codes’
unique
identification
by means of
‘instance
unique
identifiers’
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Further details about previous sections
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
OBO Foundry
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
OBO Foundry principles (1)
• The ontology must be open and available to be used by all
without any constraint other than
– (a) its origin must be acknowledged and
– (b) it is not to be altered and subsequently redistributed under
the original name or with the same identifiers.
• The ontology is in, or can be expressed in, a common
shared syntax. This may be either the OBO syntax,
extensions of this syntax, or OWL.
• Each Foundry ontology should be built on the basis of
BFO top-level distinctions
– cave: OWL-DL is not capable of representing all BFO aspects
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
OBO Foundry principles (2)
• The ontologies have a unique identifier space within the
OBO Foundry.
• The source of a representational unit (RU) from any
ontology can be immediately identified by the prefix of
the identifier of each term.
• The ontology provider has procedures for identifying
distinct successive versions.
• The ontology has a clearly specified and clearly
delineated content.
– The ontology must be orthogonal to other ontologies already
lodged within OBO.
– community acceptance of a single ontology for one domain
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
OBO Foundry principles (3)
• The ontologies include textual definitions for all RUs.
– RUs should be defined so that their precise meaning within the
context of a particular ontology is clear to a human reader.
– Textual definitions will use the genus-species form: An A =def.
a B which Cs, where B is the parent of the defined term A and C
is the defining characteristic of those Bs which are also As.
• The ontology uses relations which are unambiguously
defined following the pattern of definitions laid down in
the OBO Relation Ontology.
• The ontology is well documented.
• The ontology has a plurality of independent users.
• The ontology will be developed collaboratively with other
OBO Foundry members.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
OBO Foundry principles (4)
• Single is_a inheritance: ontologies will distinguish
a backbone ('asserted') is_a hierarchy subject to
the principle of single inheritance (each term in the
ontology has maximally one is_a parent in this
asserted hierarchy).
• Instantiability: RUs in an ontology should
correspond to instances in reality.
Ontology
Scope
R T U New York State
Cell Ontology
(CL)
URL
Centercellof
Excellence in obo.sourceforge.net/cgitypes from prokaryotes
to mammals
bin/detail.cgi?cell
Bioinformatics
& Life Sciences
Chemical Entities of Biological Interest (ChEBI)
molecular entities
Common Anatomy Reference Ontology (CARO)
Custodians
Jonathan Bard, Michael
Ashburner, Oliver Hofman
ebi.ac.uk/chebi
Paula Dematos,
Rafael Alcantara
anatomical structures in
human and model organisms
(under development)
Melissa Haendel, Terry
Hayamizu, Cornelius Rosse,
David Sutherland,
Foundational Model of
Anatomy (FMA)
structure of the human body
fma.biostr.washington.
edu
JLV Mejino Jr.,
Cornelius Rosse
Functional Genomics
Investigation Ontology
(FuGO)
design, protocol, data
instrumentation, and analysis
fugo.sf.net
FuGO Working Group
Gene Ontology
(GO)
cellular components,
molecular functions,
biological processes
www.geneontology.org
Gene Ontology Consortium
Phenotypic Quality
Ontology
(PaTO)
qualities of biomedical entities
obo.sourceforge.net/cgi
-bin/ detail.cgi?
attribute_and_value
Michael Ashburner, Suzanna
Lewis, Georgios Gkoutos
Protein Ontology
(PrO)
protein types and
modifications
(under development)
Protein Ontology Consortium
Relation Ontology (RO)
relations
obo.sf.net/relationship
Barry Smith, Chris Mungall
RNA Ontology
(RnaO)
three-dimensional RNA
structures
(under development)
RNA Ontology Consortium
Sequence Ontology
properties and features of
nucleic sequences
song.sf.net
Karen Eilbeck
http://ontologist.com
(SO)
84
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Ontology for General Medical Science
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Ontological descriptions for medical jargon (1)
• Manifestation of a Disease =def. – A bodily feature of a patient that is (a) a
deviation from clinical normality that exists in virtue of the realization of a
disease and (b) is observable.
– Observability includes observable through elicitation of response or through
the use of special instruments.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Bodily Feature
• may denote a physical component, a bodily quality, or a
bodily process.
Independent
Quality
do not have
corresponding
universals
isa
Fever
Process
continuant
isa
isa
isa
Edema
Rash
Tremor
extension_of
bodily features
rashes
signs of infectious
disease
infectious
fevers
allergic
rashes
edemas
fevers
infectious
rashes
tremors
orthostatic
tremors
signs of
Graves’
disease
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Ontological descriptions for medical jargon (2)
• Manifestation of a Disease =def. – A bodily feature of a patient that is (a) a
deviation from clinical normality that exists in virtue of the realization of a
disease and (b) is observable.
– Observability includes observable through elicitation of response or through
the use of special instruments.
• Preclinical Manifestation of a Disease =def. – A manifestation of a disease that
exists prior to its becoming detectable in a clinical history taking or physical
examination.
• Clinical Manifestation of a Disease =def. – A manifestation of a disease that is
detectable in a clinical history taking or physical examination.
• Phenotype =def. – A (combination of) bodily feature(s) of an organism
determined by the interaction of its genetic make-up and environment.
• Clinical Phenotype =def. – A clinically abnormal phenotype.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
A well-formed diagnosis of ‘pneumococal pneumonia’
• A configuration of
Disease
representational units;
isa
• Believed to mirror the
person’s disease;
Pneumococcal pneumonia
• Believed to mirror the
disease’s cause;
Instance-of at t1
• Refers to the universal
of which the disease is
#78
#56
John’s relevant caused
John’s
believed to be an
portion
by
Pneumonia
of pneumococs
instance.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Some motivations and consequences (1)
• No use of debatable or ambiguous notions such as
proposition, statement, assertion, fact, ...
• The same diagnosis can be expressed in various
forms.
Disease
isa
Pneumococcal pneumonia
Instance-of at t1
#78
caused
by
#56
Portion of
pneumococs
caused
by
isa
Pneumonia
Instance-of
Instance-of at t1
at t1
#56
caused
by
#78
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Distinct but similar diagnoses
Pneumococcal pneumonia
Instance-of at t1
#78
John’s portion
of pneumococs
caused
by
Instance-of at t2
#56
#956
John’s
Pneumonia
Bob’s
pneumonia
caused
by
#2087
Bob’s portion
of pneumococs
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Some motivations and consequences (3)
• Allows evenly clean interpretations for the wealth
of ‘modified’ diagnoses:
– With respect to the author of the representation:
• ‘nursing diagnosis’, ‘referral diagnosis’
– When created:
• ‘post-operative diagnosis’, ‘admitting diagnosis’, ‘final
diagnosis’
– Degree of belief:
• ‘uncertain diagnosis’, ‘preliminary diagnosis’
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Use of ontology in data collection
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Two distinct (?) sorts of relevant entities
Characteristics
Cases
ch1
ch2
ch3
ch4
ch5
ch6
case1
case2
case3
case4
case5
case6
...
phenotypic
genotypic
...
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Genotype / Phenotype
Gene Ontology
genes
Human Phenotype ‘Ontology’
gene products
features
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
The Gene Ontology components
• Molecular Function = elemental activity/task
– the tasks performed by individual gene products; examples are
carbohydrate binding and ATPase activity
• Biological Process = biological goal or objective
– broad biological goals, such as mitosis or purine metabolism,
that are accomplished by ordered assemblies of molecular
functions
• Cellular Component = location or complex
– subcellular structures, locations, and macromolecular
complexes; examples include nucleus, telomere, and RNA
polymerase II holoenzyme
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Application of good ontological principles
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Human Phenotype ‘Ontology’
http://www.humanphenotypeontology.org/index.
php/hpo_home.html