bfo, snomed and disease barry smith ihtsdo, bethesda, october 8, 2009 1
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BFO, SNOMED and Disease
Barry Smith
IHTSDO, Bethesda, October 8 , 2009
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2with acknowledgements to NLM: 1R21LM009824-01A1
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infectious agentis_a navigational concept
with acknowledgements to NLM: 1R21LM009824-01A1
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infectious agentis_a navigational concept
5with acknowledgements to NLM: 1R21LM009824-01A1
6with acknowledgements to NLM: 1R21LM009824-01A1
7with acknowledgements to NLM: 1R21LM009824-01A1
8with acknowledgements to NLM: 1R21LM009824-01A1
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10with acknowledgements to NLM: 1R21LM009824-01A1
General comments
Problems with ‘concept’
(no real coherence as to what SNOMED is representing)
Mixing of singulars and plurals
Confusion of disorder (continuants) with etiological and diagnostic processes (occurrents) and information entities (‘findings’)
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Epistemology and Time (from Bill Hogan)
• According to SNOMED-CT User Guide (p. 42):Concepts in [the Clinical Finding] hierarchy represent
the result of a clinical observation, assessment, or judgment, and include both normal and abnormal clinical states.
• So, does a date/time associated with a ‘finding’ refer to:– Date/time that the observation, assessment, or
judgment occurred and thus the result was obtained– Date/time that the entity (that was found) began to
exist– Date/time that entity (that was found) began to
manifest in symptoms, signs, etc.
Epistemology and Combinatorial Explosion (from Bill Hogan)
• Epistaxis/nosebleed– Epistaxis (disorder)– Nosebleed/epistaxis symptom (finding)– On examination - epistaxis (disorder)– Has nosebleeds - epistaxis (disorder)– Evidence of recent epistaxis (finding)
Epistemology and Combinatorial Explosion Explosion (from Bill Hogan)• Rash
– Cutaneous eruption (morphologic abnormality), with synonym Rash
– Eruption of skin (disorder), with synonym Rash– Complaining of a rash (finding)– On examination - a rash (finding)
• Dry skin– Dry skin (finding)– Complaining of dry skin (finding)– On examination - dry skin (finding)– Dry skin dermatitis (disorder)
128477000 Abscess (disorder)
44132006 Abscess (morphologic abnormality)
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BFO
A simple top-level ontology to support information integration in scientific research
No abstracta
Nothing propositional
No overlap with domain ontologies (for society, for information, …) – built by populating downwards
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Basic Formal Ontology
Continuant Occurrent(Process, Event)
IndependentContinuant
DependentContinuant
http://ifomis.uni-saarland.de/bfo/17
Benefits of coordination
No need to reinvent the wheel
Can profit from lessons learned through mistakes made by others
Can more easily reuse what is made by others
Can more easily inspect and criticize results of others’ work (PATO)
Leads to innovations (e.g. Mireot) in strategies for combining ontologies
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Users of BFO
NCI BiomedGT
SNOMED CT
Ontology for General Medical Science (OGMS)
ACGT Clinical Genomics Trials on Cancer – Master Ontology / Formbuilder (Case Report Forms for Cancer Clinical Trials)
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Users of BFO
MediCognos / Microsoft Healthvault
Cleveland Clinic Semantic Database in Cardiothoracic Surgery
Major Histocompatibility Complex (MHC) Ontology (NIAID)
Neuroscience Information Framework Standard (NIFSTD) and Constituent Ontologies
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Users of BFO
Interdisciplinary Prostate Ontology (IPO)
Nanoparticle Ontology (NPO): Ontology for Cancer Nanotechnology Research
Neural Electromagnetic Ontologies (NEMO)
ChemAxiom – Ontology for Chemistry
Ontology for Risks Against Patient Safety (RAPS/REMINE) (EU FP7)
IDO Infectious Disease Ontology (NIAID)
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IDO Consortium
• MITRE, Mount Sinai, UTSouthwestern – Influenza
• IMBB/VectorBase – Vector borne diseases (A. gambiae, A. aegypti, I. scapularis, C. pipiens, P. humanus)
• Colorado State University – Dengue Fever
• Duke University – Tuberculosis, Staph. aureus
• Case Western Reserve – Infective Endocarditis
• University of Michigan – Brucilosis
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– GO Gene Ontology– CL Cell Ontology– SO Sequence Ontology– ChEBI Chemical Ontology – PATO Phenotype (Quality) Ontology– FMA Foundational Model of Anatomy– ChEBI Chemical Entities of Biological Interest – CARO Common Anatomy Reference Ontology – PRO Protein Ontology– Infectious Disease Ontology– Plant Ontology– Environment Ontology– Ontology for Biomedical Investigations– RNA Ontology
The OBO Foundry
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RELATION TO TIME
GRANULARITY
CONTINUANT OCCURRENT
INDEPENDENT DEPENDENT
ORGAN ANDORGANISM
Organism(NCBI
Taxonomy)
Anatomical Entity(FMA, CARO)
OrganFunction
(FMP, CPRO) Phenotypic
Quality(PaTO)
Biological Process
(GO)CELL AND CELLULAR
COMPONENT
Cell(CL)
Cellular Compone
nt(FMA, GO)
Cellular Function
(GO)
MOLECULEMolecule
(ChEBI, SO,RnaO, PrO)
Molecular Function(GO)
Molecular Process
(GO)
The Open Biomedical Ontologies (OBO) Foundry24
RELATION TO TIME
GRANULARITY
CONTINUANT OCCURRENT
INDEPENDENT DEPENDENT
COMPLEX OF ORGANISMS
Family, Community,
Deme, Population OrganFunction
(FMP, CPRO)
Population
Phenotype
Population Process
ORGAN ANDORGANISM
Organism(NCBI
Taxonomy)
(FMA, CARO)
Phenotypic Quality(PaTO)
Biological Process
(GO)CELL AND CELLULAR
COMPONENT
Cell(CL)
Cell Com-
ponent(FMA, GO)
Cellular Function
(GO)
MOLECULEMolecule
(ChEBI, SO,RnaO, PrO)
Molecular Function(GO)
Molecular Process
(GO)
E N
V I R
O N
M E
N T
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CONTINUANT OCCURRENT
INDEPENDENT DEPENDENT
ORGAN ANDORGANISM
Organism(NCBI
Taxonomy)
Anatomical Entity
(FMA, CARO)
OrganFunction
(FMP, CPRO) Phenotypic
Quality(PaTO)
Organism-Level Process
(GO)
CELL AND CELLULAR
COMPONENT
Cell(CL)
Cellular Compone
nt(FMA, GO)
Cellular Function
(GO)
Cellular Process
(GO)
MOLECULEMolecule
(ChEBI, SO,RNAO, PRO)
Molecular Function(GO)
Molecular Process
(GO)
rationale of OBO Foundry coverage (homesteading principle)
GRANULARITY
RELATION TO TIME
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BFO and the 3 Gene Ontologies (GO)
Continuant Occurrent
IndependentContinuant
DependentContinuant
cell component
biological process
molecular function
Kumar A., Smith B, Borgelt C. Dependence relationships between Gene Ontology terms based on TIGR gene product annotations. CompuTerm 2004, 31-38.
Bada M, Hunter L. Enrichment of OBO Ontologies. J Biomed Inform. 2006 Jul 26
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OBO Foundry organized in terms of Basic Formal Ontology
Each Foundry ontology can be seen as an extension of a single upper level ontology (BFO)
either post hoc, as in the case of the GO
or in virtue of creation ab initio via downward population from BFO
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Example: The Cell Ontology
Continuant
IndependentContinuant
DependentContinuant
..... .....
Non-realizableDependentContinuant(quality)
Realizable DependentContinuant(function, role, disposition)
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Realizable dependent continuants
plan
function
role
disposition
capability
tendency
continuants
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Their realizations
execution
expression
exercise
realization
application
course
occurrents
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Continuant
IndependentContinuant
DependentContinuant
..... .....
Non-realizableDependentContinuant(quality)
Realizable DependentContinuant(function, role, disposition)
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realization depends_on realizable
Continuant Occurrent
IndependentContinuant
bearer
DependentContinuant
disposition
.... ..... .......34
Process of realization
Specific Dependenceon the instance level
a depends_on b =def. a is necessarily such that if b ceases to exist than a ceases to exist
on the type level
A specifically_depends_on B =def. for every instance a of A, there is some instance b of B such that a depends_on b.
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depends_on
Continuant Occurrent
process, eventIndependentContinuant
thing
DependentContinuant
quality
.... ..... .......temperature dependson bearer
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Specifically dependent continuants
• the quality of whiteness of this cheese
• your role as lecturer
• the disposition of this patient to experience diarrhea
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the particular case of redness (of a particular fly eye)
the universal red
instantiates
an instance of an eye (in a particular fly)
the universal eye
instantiates
depends_on
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the particular case of redness (of a particular fly eye)
red
instantiates
an instance of an eye (in a particular fly)
eye
instantiates
depends on
color anatomical structure
is_a is_a
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depends_on
Continuant Occurrent
process
IndependentContinuant
thing
DependentContinuant
quality
.... ..... .......temperature dependson bearer
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Specifically Dependent Continuants
SpecificallyDependentContinuant
Quality, Pattern
Realizable Dependent Continuant
if the bearer ceases to exist, then its quality, function, role ceases to exist
the color of my skin
the function of my heart to pump blood
my weight41
Generically Dependent Continuants
GenericallyDependentContinuant
Information Object
Gene Sequence
if one bearer ceases to exist, then the entity can survive, because there are other bearers
(copyability)
the pdf file on my laptop
the DNA (sequence) in this chromosome 42
Continuant Occurrent
IndependentContinuant
SpecificallyDependentContinuant
Quality
Disposition
Functioning
Function
GenericallyDependentContinuant
Realizable
Role
Information Artifact
Sequence…
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Realizable dependent continuants
Role: nurse role, pathogen role, food role
Disposition: fragility, virulence, susceptibility, genetic disposition to disease X
Function: to pump (of the heart), to unlock (of the key)
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Role (Externally-Grounded Realizable Entity)
role =def. a realizable entity
• which exists because the bearer is in some special physical, social, or institutional set of circumstances in which the bearer does not have to be, and
• is not such that, if it ceases to exist, then the physical make-up of the bearer is thereby changed.
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Disposition (Internally-Grounded Realizable Entity)
disposition =def.
a realizable entity which if it ceases to exist, then its bearer is physically changed, and
whose realization occurs when this bearer is in some special physical circumstances, in virtue of the bearer’s physical make-up
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Function (A Disposition Designed or Selected For)
function =def.
a disposition that
exists in virtue of the bearer’s physical make-up,,
and
this physical make-up is something the bearer possesses because it came into being, either through evolution (in the case of natural biological entities) or through intentional design (in the case of artifacts), in order to realize processes of a certain kind.
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Four distinct classificatory tasks
1. of people (patients, carriers, …)
2. of diseases (cases, instances, problems, …)
3. of courses of disease (symptoms, treatments…)
4. of representations (records, observations, data, diagnoses…)
ICD confuses 1. & 2.
HL7, most standard terminologies, confuse 2. and 4
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Four distinct BFO categories
1. person (patient, carrier, …) – independent continuant
2. disease (case, instance, problem, …) – specifically dependent continuant
3. course of disease (symptom, treatment…)– occurrent
4. representation (record, datum, diagnosis…)– generically dependent continuant
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Four distinct BFO categories
1. people (patients, carriers, …) – independent continuants
2. disease (case, instance, problem, condition …) – disposition
3. course of disease (symptom, episode, outbreak …)– realization of dispositions
4. representations (records, data, diagnoses…)– generically dependent continuants
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Disposition
Internally-Grounded Realizable Entity
A disposition is
a realizable entity which is such that, if it ceases to exist, then its bearer is physically changed,
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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Disorder
1. person
– independent continuantobjects
fiat object part
object aggregate
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Disorder
A fiat object part of an organism which serves as the bearer of a disposition of a certain sort
This fiat object may have no determinate boundaries
(compare: Downtown Santa Barbara)
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Where does Mount Everest begin and end?Cf. Barry Smith and David M. Mark, “Do Mountains Exist?”, Environment and Planning B, 30, 2003.
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Big Picture (with thanks to Richard Scheuermann)
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A disease is a disposition rooted in a
physical disorder in the organism and
realized in pathological processes.
etiological process
produces
disorder
bears
disposition
realized_in
pathological process
produces
abnormal bodily features
recognized_as
signs & symptomsinterpretive process
produces
diagnosis
used_in58
Elucidation of Primitive Terms ‘bodily feature’ - an abbreviation for a physical
component, a bodily quality, or a bodily process. disposition - an attribute describing the propensity to
initiate certain specific sorts of processes when certain conditions are satisfied.
clinically abnormal - some bodily feature that (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.*
*Compare: baldness59
Definitions - Foundational Terms
Disorder =def. – A causally linked combination of physical components that is clinically abnormal.
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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Dispositions and Predispositions
All diseases are dispositions; not all dispositions are diseases. A predisposition is a disposition. Predisposition to Disease of Type X =def. – A disposition in an
organism that constitutes an increased risk of the organism’s subsequently developing the disease X.
HNPCC is caused by a disorder (mutation) in a DNA mismatch repair gene that disposes to the acquisition of additional mutations from
defective DNA repair processes, and thus is a predisposition to the development of colon cancer.
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Definitions - Clinical Evaluation Terms
Sign =def. – A bodily feature of a patient that is observed in a physical examination and is deemed by the clinician to be of clinical significance. (Objectively observable features)
Symptom =def. – A experienced bodily feature of a patient that is observed by and observable only by the patient and is of the type that can be hypothesized by a patient to be a realization of a disease. (A restricted family of phenomena including pain, nausea, anger, drowsiness, which are of their nature experienced in the first person)
Symptoms are subjective. But this does not mean that there is no objective fact of the matter whether a given symptom exists
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Cirrhosis - environmental exposure Etiological process - phenobarbitol-
induced 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 - 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 - 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 results in the elimination of the disorder (transient disease course).
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Huntington’s Disease - genetic Etiological process - inheritance of
>39 CAG repeats in the HTT gene produces
Disorder - chromosome 4 with abnormal mHTT bears
Disposition (disease) - Huntington’s disease realized_in
Pathological process - accumulation of mHTT protein fragments, abnormal transcription regulation, neuronal cell death in striatum produces
Abnormal bodily features recognized_as
Symptoms - anxiety, depression Signs - difficulties in speaking and
swallowing
Symptoms & Signs used_in
Interpretive process produces
Hypothesis - rule out Huntington’s suggests
Laboratory tests produces
Test results - molecular detection of the HTT gene with >39CAG repeats used_in
Interpretive process produces
Result - diagnosis that patient X has a disorder that bears the disease Huntington’s disease
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HNPCC - genetic pre-disposition
Etiological process - inheritance of a mutant mismatch repair gene produces
Disorder - chromosome 3 with abnormal hMLH1 bears
Disposition (disease) - Lynch syndrome realized_in
Pathological process - abnormal repair of DNA mismatches produces
Disorder - mutations in proto-oncogenes and tumor suppressor genes with microsatellite repeats (e.g. TGF-beta R2) bears
Disposition (disease) - non-polyposis colon cancer realized in
Symptoms (including pain)
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Definition: Etiology
Etiological Process =def. – A process in an organism that leads to a subsequent disorder.
Example: toxic chemical exposure resulting in a mutation in the genomic DNA of a cell; infection of a human with a pathogenic virus; inheritance of two defective copies of a metabolic gene
The etiological process creates the physical basis of that disposition to pathological processes which is the disease.
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Definitions - 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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Definitions - Qualities
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.
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