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Basic Building Blocks for
Biomedical Ontologies
Barry Smith
1
Problems with UMLS-style
approaches
• let a million ontologies bloom, each one close
to the terminological habits of its authors
• in concordance with the “not invented here”
syndrome
• then map these ontologies, and use these
mappings to integrate your different pots of
data
2
Mappings are hard
They create an N2 problem; are fragile, and
expensive to maintain
Need new authorities to maintain(one for each
pair of mapped ontologies), yielding new risk
of forking – who will police the mappings?
The goal should be to minimize the need for
mappings, by avoiding redundancy in the first
place – one ontology for each domain
Invest resources in disjoint ontology modules
which work well together – reduce need for
mappings to minimum possible
8
Why should you care?
• you need to create systems for data mining
and text processing which will yield useful
digitally coded output
• if the codes you use are constantly in need of
ad hoc repair huge, resources will be wasted
• serious investment in annotation will be
defeated from the start
• relevant data will not be found, because it will
be lost in multiple semantic cemeteries
9
How to do it right?
• how create an incremental, evolutionary process,
where what is good survives, and what is bad
fails
• where the number of ontologies needing to be
used together is small – integration = addition
• where these ontologies are stable
• by creating a scenario in which people will find it
profitable to reuse ontologies, terminologies and
coding systems which have been tried and tested
10
Reasons why GO has been
successful
It is a system for prospective standardization
built with coherent top level but with content
contributed and monitored by domain specialists
Based on community consensus
Updated every night
Clear versioning principles ensure backwards
compatibility; prior annotations do not lose their
value
Initially low-tech to encourage users, with
movement to more powerful formal approaches
(including OWL-DL – though still proceeding
caution)
11
GO has learned the lessons of
successful cooperation
• Clear documentation
• The terms chosen are already familiar
• Fully open source (allows thorough testing in
manifold combinations with other ontologies)
• Subjected to considerable third-party critique
• Tracker for user input and help desk with rapid
turnaround
12
GO has been amazingly successful in
overcoming the data balkanization
problem
but it covers only generic biological entities of
three sorts:
– cellular components
– molecular functions
– biological processes
no diseases, symptoms, disease biomarkers,
protein interactions, experimental processes …
13
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)
OBO (Open Biomedical Ontology) Foundry proposal
(Gene Ontology in yellow)
14
RELATION
TO TIME
CONTINUANT
INDEPENDENT
OCCURRENT
DEPENDENT
ORGAN AND
ORGANISM
CELL AND
CELLULAR
COMPONENT
MOLECULE
Organism
(NCBI
Taxonomy)
Anatomical
Entity
(FMA,
CARO)
Cell
(CL)
Cellular
Component
(FMA, GO)
Molecule
(ChEBI, SO,
RnaO, PrO)
Environment Ontology
(ENVO)
GRANULARITY
Organ
Function
(FMP, CPRO)
Phenotypic
Quality
(PaTO)
Biological
Process
(GO)
Cellular
Function
(GO)
Molecular Function
(GO)
Molecular Process
(GO)
Environment Ontology
15
RELATION
TO TIME
CONTINUANT
INDEPENDENT
OCCURRENT
DEPENDENT
GRANULARITY
COMPLEX OF
ORGANISMS
ORGAN AND
ORGANISM
CELL AND
CELLULAR
COMPONENT
MOLECULE
Family, Community,
Deme, Population
Population
Phenotype
Organ
Anatomical
Function
Organism
Entity
(FMP, CPRO)
(NCBI
(FMA,
Phenotypic
Taxonomy)
CARO)
Quality
(PaTO)
Cellular
Cellular
Cell
Component Function
(CL)
(FMA, GO)
(GO)
Molecule
(ChEBI, SO,
RnaO, PrO)
Molecular Function
(GO)
Population-level ontologies
Population
Process
Biological
Process
(GO)
Molecular Process
(GO)
16
The OBO Foundry: a step-by-step,
evidence-based approach to
expanding the GO
 Developers commit to working to ensure
that, for each domain, there is community
convergence on a single ontology
 and agree in advance to collaborate with
developers of ontologies in adjacent
domains.
http://obofoundry.org
17
OBO Foundry Principles
 Common governance (coordinating editors)
 Common training
 Common architecture:
• simple shared top level ontology (BFO)
• shared Relation Ontology:
www.obofoundry.org/ro
18
Open Biomedical Ontologies Foundry
Seeks to create high quality, validated terminology
modules across all of the life sciences which will be
• one ontology for each domain, so no need for
mappings
• close to language use of experts
• evidence-based
• incorporate a strategy for motivating potential
developers and users
• revisable as science advances
19
Principles
http://obofoundry.org/wiki/index.php/OBO_Foundry
Principles
20
RELATION TO
TIME
GRANULARITY
INDEPENDENT
ORGAN AND
ORGANISM
Organism
(NCBI
Taxonomy)
CELL AND
CELLULAR
COMPONENT
Cell
(CL)
MOLECULE
CONTINUANT
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)
Organism-Level
Process
(GO)
Cellular Process
(GO)
Molecular
Process
(GO)
OBO Foundry coverage
21
ORTHOGONALITY
modularity ensures
•
•
•
•
•
annotations can be additive
division of labor amongst domain experts
high value of training in any given module
lessons learned in one module can benefit
work on other modules
incentivization of those responsible for
individual modules
22
Benefits of coordination
•
•
•
Can more easily reuse what is made by others
Can more easily inspect and criticize what is
made by others
Leads to innovations (e.g. Mireot strategy for
importing terms into ontologies)
23
RELATION
TO TIME
CONTINUANT
INDEPENDENT
OCCURRENT
DEPENDENT
GRANULARITY
ORGAN AND
ORGANISM
Organism
(NCBI
Taxonomy)
CELL AND
CELLULAR
COMPONENT
Cell
(CL)
Anatomical
Entity
(FMA,
CARO)
Organ
Function
(FMP, CPRO) Phenotypic
Quality
XAO ZFA
(PaTO)
Cellular
Component
(FMA, GO)
Molecule (SO, RnaO)
MOLECULE
ChEBI
PRO
Biological
Process
(GO)
Cellular
Function
(GO)
Molecular Function
(GO)
Molecular
Process
(GO)
Current Foundry members in yellow
24
Foundry ontologies currently under
review
Plant Ontology (PO)
Ontology for Biomedical Investigations (OBI)
Ontology for General Medical Science (OBMS)
Infectious Disease Ontology (IDO)
25
top level
mid-level
Basic Formal Ontology (BFO)
Information Artifact
Ontology
(IAO)
Ontology for Biomedical
Investigations
(OBI)
Anatomy Ontology
(FMA*, CARO)
Cell
Ontology
(CL)
domain level
Cellular
Component
Ontology
(FMA*, GO*)
Environment
Ontology
(EnvO)
Subcellular Anatomy Ontology (SAO)
Sequence Ontology
(SO*)
Protein Ontology
(PRO*)
Ontology of General
Medical Science
(OGMS)
Infectious
Disease
Ontology
(IDO*)
Phenotypic
Quality
Ontology
(PaTO)
Biological
Process
Ontology (GO*)
Molecular
Function
(GO*)
OBO Foundry Modular Organization
26
OBI
The Ontology for Biomedical Investigations
hfp://purl.org/obo/OBI_0000225
27
Purpose of OBI
To provide a resource for the unambiguous
description of the components of
biomedical investigations such as the
design, protocols and instrumentation,
material, data and types of analysis and
statistical tools applied to the data
 NOT designed to model biology
28
OBI Collaborating Communities
Crop sciences Generation Challenge Programme (GCP),
Environmental genomics MGED RSBI Group,
www.mged.org/Workgroups/rsbi
Genomic Standards Consortium (GSC),
www.genomics.ceh.ac.uk/genomecatalogue
HUPO Proteomics Standards Initiative (PSI), psidev.sourceforge.net
Immunology Database and Analysis Portal, www.immport.org
Immune Epitope Database and Analysis Resource (IEDB),
http://www.immuneepitope.org/home.do
International Society for Analytical Cytology, http://www.isac-net.org/
Metabolomics Standards Initiative (MSI),
Neurogenetics, Biomedical Informatics Research Network (BIRN),
Nutrigenomics MGED RSBI Group, www.mged.org/Workgroups/rsbi
Polymorphism
Toxicogenomics MGED RSBI Group, www.mged.org/Workgroups/rsbi
Transcriptomics MGED Ontology Group
29
30
31
32
33
Ontology for General Medical
Science
http://code.google.com/p/ogms/
(OBO) http://purl.obolibrary.org/obo/ogms.obo
(OWL) http://purl.obolibrary.org/obo/ogms.owl
34
OGMS-based initiatives
Vital Signs Ontology (VSO) (Welch Allyn)
EHR / Demographics Ontology
Infectious Disease Ontology
Mental Health Ontology
Emotion Ontology
35
Ontology for General Medical
Science
Jobst Landgrebe (then Co-Chair of the HL7
Vocabulary Group):
“the best ontology effort in the whole
biomedical domain by far”
36
EXPERIMENTAL
ARTIFACTS
Ontology for Biomedical Investigations (OBI)
CLINICAL
MEDICINE
Ontology of General Medical Science (OGMS)
INFORMATION
ARTIFACTS
Information Artifact Ontology (IAO)
How to keep clear about the distinction
• processes of observation,
• results of such processes (measurement
data)
• the entities observed
37
How is the OBO Foundry organized?
• Top-Level: Basic Formal Ontology (BFO)
• Mid-Level: IAO, OBI, OGMS ...
• Domain-Level: Foundry Bio-Ontologies
38
top level
mid-level
Basic Formal Ontology (BFO)
Information Artifact
Ontology
(IAO)
Ontology for Biomedical
Investigations
(OBI)
Anatomy Ontology
(FMA*, CARO)
Cell
Ontology
(CL)
domain level
Cellular
Component
Ontology
(FMA*, GO*)
Environment
Ontology
(EnvO)
Subcellular Anatomy Ontology (SAO)
Sequence Ontology
(SO*)
Protein Ontology
(PRO*)
Ontology of General
Medical Science
(OGMS)
Infectious
Disease
Ontology
(IDO*)
Phenotypic
Quality
Ontology
(PaTO)
Biological
Process
Ontology (GO*)
Molecular
Function
(GO*)
OBO Foundry Modular Organization
39
BFO: the very top
Continuant
Independent
Continuant
Occurrent
(Process, Event)
Dependent
Continuant
40
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)
41
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)
obofoundry.org
Organism-Level
Process
(GO)
Cellular Process
(GO)
Molecular
Process
(GO)
42
BFO & GO
continuant
independent
continuant
dependent
continuant
cellular
component
molecular
function
occurrent
biological
processes
43
Basic Formal Ontology
types
Continuant
Independent
Continuant
Dependent
Continuant
thing
quality
Occurrent
process, event
.... ..... .......
instances
44
Experience with BFO in
building ontologies provides
• a community of skilled ontology developers
and users (user group has 120 members)
• associated logical tools
• documentation for different types of users
• a methodology for building conformant
ontologies by starting with BFO and populating
downwards
45
Example: The Cell Ontology
How to build an ontology
import BFO into ontology editor such as Protégé
work with domain experts to create an initial midlevel classification
find ~50 most commonly used terms corresponding
to types in reality
arrange these terms into an informal is_a hierarchy
according to this universality principle
A is_a B  every instance of A is an instance of B
fill in missing terms to give a complete hierarchy
(leave it to domain experts to populate the lower
levels of the hierarchy)
47
Users of BFO
PharmaOntology (W3C HCLS SIG)
MediCognos / Microsoft Healthvault
Cleveland Clinic Semantic Database in Cardiothoracic
Surgery
Major Histocompatibility Complex (MHC) Ontology (NIAID)
Neuroscience Information Framework Standard (NIFSTD)
and Constituent Ontologies
Interdisciplinary Prostate Ontology (IPO)
Nanoparticle Ontology (NPO): Ontology for Cancer
Nanotechnology Research
Neural Electromagnetic Ontologies (NEMO)
ChemAxiom – Ontology for Chemistry
49
:.
Users of BFO
GO Gene Ontology
CL Cell Ontology
SO Sequence Ontology
ChEBI Chemical Ontology
PATO Phenotype (Quality) Ontology
FMA Foundational Model of Anatomy Ontology
ChEBI Chemical Entities of Biological Interest
PRO Protein Ontology
Plant Ontology
Environment Ontology
Ontology for Biomedical Investigations
RNA Ontology
:.
50
Users of BFO
Ontology for Risks Against Patient Safety (RAPS/REMINE)
eagle-i an VIVO (NCRR)
IDO Infectious Disease Ontology (NIAID)
National Cancer Institute Biomedical Grid Terminology
(BiomedGT)
US Army Biometrics Ontology
US Army Command and Control Ontology
Sleep Domain Ontology
Subcellular Anatomy Ontology (SAO)
Translaftional Medicine On (VO)
Yeast Ontology (yOWL)
Zebrafish Anatomical Ontology (ZAO)
51
:.
Basic Formal Ontology
continuant
independent
continuant
occurrent
dependent
continuant
organism
54
Continuants
• continue to exist through time,
preserving their identity while
undergoing different sorts of changes
• independent continuants – objects,
things, ...
• dependent continuants – qualities,
attributes, shapes, potentialities ...
55
Occurrents
• processes, events, happenings
– your life
– this process of accelerated cell division
56
Qualities
temperature
blood pressure
mass
...
are continuants
they exist through time while
undergoing changes
57
Qualities
temperature / blood pressure / mass ...
are dimensions of variation within the
structure of the entity
a quality is something which can
change while its bearer remains one
and the same
58
A Chart representing how
John’s temperature changes
59
A Chart representing how
John’s temperature changes
60
BFO: The Very Top
continuant
independent
continuant
occurrent
dependent
continuant
quality
temperature
62
Blinding Flash of the Obvious
independent
continuant
dependent
continuant
quality
organism
John
temperature
John’s
temperature
types
instances
63
Blinding Flash of the Obvious
independent
continuant
dependent
continuant
quality
organism
John
temperature
John’s
temperature
types
instances
64
Blinding Flash of the Obvious
inheres_in
organism
John
temperature
John’s
temperature
types
instances
65
types
temperature
37ºC
instantiates
at t1
37.1ºC
instantiates
at t2
37.2ºC
instantiates
at t3
37.3ºC
instantiates
at t4
37.4ºC
instantiates
at t5
37.5ºC
instantiates
at t6
John’s temperature
instances
66
types
human
embryo
instantiates
at t1
fetus
instantiates
at t2
neonate
instantiates
at t3
infant
child
instantiates
at t4
instantiates
at t5
adult
instantiates
at t6
John
instances
67
Temperature subtypes
Development-stage subtypes
are threshold divisions (hence we do
not have sharp boundaries, and we
have a certain degree of choice, e.g. in
how many subtypes to distinguish,
though not in their ordering)
68
independent
continuant
dependent
continuant
quality
organism
John
temperature
types
John’s
temperature
instances
69
independent
continuant
organism
John
dependent
continuant
occurrent
quality
process
temperature
John’s
temperature
course of
temperature
changes
John’s
temperature history
70
independent
continuant
organism
John
dependent
continuant
occurrent
quality
process
temperature
John’s
temperature
life of an
organism
John’s
life
71
BFO: The Very Top
continuant
independent
continuant
occurrent
dependent
continuant
quality
disposition
72
BFO: The Very Top
continuant
independent
continuant
occurrent
dependent
continuant
quality
function
role
disposition
73
disposition
-
of
of
of
of
a glass vase, to shatter if dropped
a human, to eat
a banana, to ripen
John, to lose hair
74
disposition
if it ceases to exist, then its bearer
and/or its immediate surrounding
environment is physically changed
its realization occurs when its bearer is in
some special physical circumstances
its realization is what it is in virtue of the
bearer’s physical make-up
75
independent
continuant
eye
John’s eye
dependent
continuant
occurrent
function
process
to see
process of
seeing
function of John’s
eye: to see
John seeing
80
OGMS
Ontology for General Medical
Science
http://code.google.com/p/ogms
88
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Ontology of General Medical Science (OGMS)
• ontology for the representation of
– diseases, signs, symptoms
– clinical processes
– diagnosis, treatment and outcomes
• fundamental idea:
– a disease is a disposition rooted in some
(physical) disorder in the organism
89
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Motivation
• Clarity about:
– disease etiology and progression
– disease and the diagnostic process
– phenotype and signs/symptoms
– entities in reality and observations of sucn
entities
90
Physical Disorder
91
Physical Disorder
– independent
continuant
fiat object part
A causally linked combination
of physical components of the
extended organism that is
clinically abnormal.
92
:.
Clinically abnormal
– (1) not part of the life plan for an organism
of the relevant type (unlike aging or
pregnancy),
– (2) causally linked to an elevated risk
either of pain or other feelings of illness,
or of death or dysfunction, and
– (3) such that the elevated risk exceeds a
certain threshold level.*
*Compare: baldness
93
Big Picture
94
Pathological Process
=def. A bodily process that is a
manifestation of a disorder and is clinically
abnormal.
Disease =def. – A disposition to undergo
pathological processes that exists in an
organism because of one or more
disorders in that organism.
95
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, enlarged spleen
96
Dispositions and Predispositions
All diseases are dispositions; not all
dispositions are diseases.
Predisposition to Disease
=def. – A disposition in an organism that
constitutes an increased risk of the
organism’s subsequently developing some
disease.
97
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)
98
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
99
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
100
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 - elevated liver enzymes in
serum
 used_in
Interpretive process
 produces
Result - diagnosis that patient X has a
disorder that bears the disease
cirrhosis
101
Systemic arterial hypertension
•
•
•
•
•
•
•
Etiological process – abnormal
reabsorption of NaCl by the kidney
– produces
Disorder – abnormally large scattered
molecular aggregate of salt in the
blood
– bears
Disposition (disease) - hypertension
– realized_in
Pathological process – exertion of
abnormal pressure against arterial wall
– produces
Abnormal bodily features
– recognized_as
Symptoms - headaches, dizziness
Signs – elevated blood pressure







Symptoms & Signs
 used_in
Interpretive process
 produces
Hypothesis - rule out hypertension
 suggests
Laboratory tests
 produces
Test results  used_in
Interpretive process
 produces
Result - diagnosis that patient X has a
disorder that bears the disease hypertension
102
Type 2 Diabetes Mellitus
•
•
•
•
•
•
•
Etiological process –
– produces
Disorder – abnormal pancreatic beta
cells and abnormal muscle/fat cells
– bears
Disposition (disease) – diabetes
mellitus
– realized_in
Pathological processes – diminished
insulin production , diminished
muscle/fat uptake of glucose
– produces
Abnormal bodily features
– recognized_as
Symptoms – polydipsia, polyuria,
polyphagia, blurred vision
Signs – elevated blood glucose and
hemoglobin A1c







Symptoms & Signs
 used_in
Interpretive process
 produces
Hypothesis - rule out diabetes mellitus
 suggests
Laboratory tests – fasting serum blood
glucose, oral glucose challenge test, and/or
blood hemoglobin A1c
 produces
Test results  used_in
Interpretive process
 produces
Result - diagnosis that patient X has a
disorder that bears the disease type 2
diabetes mellitus
103
Type 1 hypersensitivity to penicillin
•
•
•
•
•
•
•
Etiological process – sensitizing of mast
cells and basophils during exposure to
penicillin-class substance
– produces
Disorder – mast cells and basophils with
epitope-specific IgE bound to Fc epsilon
receptor I
– bears
Disposition (disease) – type I
hypersensitivity
– realized_in
Pathological process – type I
hypersensitivity reaction
– produces
Abnormal bodily features
– recognized_as
Symptoms – pruritis, shortness of breath
Signs – rash, urticaria, anaphylaxis







Symptoms & Signs
 used_in
Interpretive process
 produces
Hypothesis  suggests
Laboratory tests –
 produces
Test results – occasionally, skin testing
 used_in
Interpretive process
 produces
Result - diagnosis that patient X has a
disorder that bears the disease type 1
hypersensitivity to penicillin
104
105
Disease vs. Disease course
Disease =def. – A disposition to undergo
pathological processes that exists in an
organism because of one or more
disorders in that organism.
Disease course =def. – The aggregate of
processes in which a disease disposition
is realized.
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coronary heart
disease
disease
associated
with early
lesions and
small fibrous
plaques
instantiates
at t1
disease
associated with
asymptomatic
(‘silent’)
infarction
instantiates
at t2
disease
associated
with surface
disruption of
plaque
instantiates
at t3
unstable
angina
instantiates
at t4
stable
angina
instantiates
at t5
John’s coronary heart disease
time
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independent
continuant
disorder
John’s
disordered
heart
dependent
continuant
occurrent
disposition
process
disease
course of
disease
John’s
coronary heart
disease
course of John’s
disease
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Examples of ontology terms
Independent
Continuant
Dependent
Continuant
Occurrent
OGMS
IDO
Disorder
Infectious
disorder
Disease
Infectious
disease
Predisposition
to disease
Protective
resistance
Disease course
Infectious
disease course
IDO (Infectious Disease Ontology) Core
Follows GO strategy of providing a
canonical ontology of what is involved
in every infectious disease – host,
pathogen, vector, virulence, vaccine,
transmission – accompanied by IDO
Extensions for specific diseases,
pathogens and vectors
Provides common terminology resources
and tested common guidelines for a
vast array of different disease
communities
110
Infectious Disease Ontology 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
• Cleveland Clinic – Infective Endocarditis
• University of Michigan – Brucellosis
• Duke University, University at Buffalo – HIV
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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
112
Influenza – disease course
• 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 - The
acutedisorder
inflammation
also induces normal
– produces
physiological processes (immune
• Abnormal bodily features
response) that can results in the
– recognized_as
elimination of the disorder (transient
• Symptoms - weakness, dizziness
disease course).
• Signs - fever
113
Big Picture
114