BFO and Ontology Design Principles Barry Smith 1.

BFO and Ontology Design Principles

Barry Smith

1

How is the OBO Foundry organized?

• Top-Level: Basic Formal Ontology (BFO)• Mid-Level: IAO, OBI, OGMS ...• Domain-Level: Foundry Bio-Ontologies

Anatomy Ontology(FMA*, CARO)

Environment

Ontology(EnvO)

Infectious Disease

Ontology(IDO*)

Biological Process

Ontology (GO*)

Cell Ontology

(CL)

CellularComponentOntology

(FMA*, GO*) Phenotypic Quality

Ontology(PaTO)

Subcellular Anatomy Ontology (SAO)Sequence Ontology

(SO*) Molecular Function

(GO*)Protein Ontology(PRO*) OBO Foundry Modular Organization 3

top level

mid-level

domain level

Information Artifact Ontology

(IAO)

Ontology for Biomedical Investigations

(OBI)

Ontology of General Medical Science

(OGMS)

Basic Formal Ontology (BFO)

BFO: the very top

Continuant Occurrent(Process, Event)

IndependentContinuant

DependentContinuant

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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)

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)

obofoundry.org

GRANULARITY

RELATION TO TIME

BFO & GO

continuant occurrent

biological processes

independentcontinuant

cellular component

dependentcontinuant

molecular function

Basic Formal Ontology

Continuant Occurrent

process, eventIndependentContinuant

thing

DependentContinuant

quality

.... ..... .......

types

instances

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

Example: The Cell Ontology

:.

Users of BFOPharmaOntology (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

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:.

Users of BFOGO 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

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:.

Users of BFOOntology 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)

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:.

DOLCE, SUMO, Cyc

DOLCE: (Largely) extends BFO, but built to support ‘linguistic and cognitive engineering’

SUMO: No dependent continuants (so: no diabetes, no temperature instances); SUMO has its own tiny biology (‘body-covering’, ‘fruit-Or-vegetable’)

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:.

Cyc:ConceivingSomething_BiologicalReproductionEvent =def a collection of events; a sub-collection of BiologicalReproductionEvent. In each conceivingSomething_BiologicalReproduction Event, someone becomes pregnant.

Cyc:The immaculate conception =def. The ConceivingSomething_BiologicalReproductionEvent in which Mary_MotherOfJesus was conceived. Catholic dogma holds that Mary (unlike Jesus) was conceived by conventional biological means, but that GodOfAbrahamIsaacAndJacob interceded at the time of her conception to keep her free from the stain of original sin, or ‘immaculate’.

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Basic Formal Ontology



dependentcontinuant

organism

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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 ...

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Occurrents

• processes, events, happenings– your life– this process of accelerated cell

division

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Qualitiestemperatureblood pressuremass...

are continuantsthey exist through time while undergoing changes

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Qualitiestemperature / blood pressure /

mass ...are dimensions of variation within the structure of the entitya quality is something which can change while its bearer remains one and the same

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A Chart representing how John’s temperature

changes

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A Chart representing how John’s temperature

changes

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BFO: The Very Top

continuant


dependentcontinuant

quality

occurrent

temperature 26

Blinding Flash of the Obvious


dependentcontinuant

quality

temperature types

instances

organism

John John’s

temperature 27



dependentcontinuant

quality

temperature types

instances

organism

John John’s

temperature 28


temperature types

instances

organism

John John’s

temperature .

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inheres_in

temperature types

instances

John’s temperature

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37ºC37.1º

C37.5º

C37.2º

C37.3º

C37.4º

C

instantiates at t1

instantiates at t2

instantiates at t3

instantiates at t4

instantiates at t5

instantiates at t6

human types

instances

John

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embryo

fetus adultneonat

einfant child

instantiates at t1

instantiates at t2

instantiates at t3

instantiates at t4

instantiates at t5

instantiates at t6

Temperature subtypesDevelopment-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)

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dependentcontinuant

quality

temperature types

instances

organism

John John’s

temperature

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dependentcontinuant

quality

temperature

organism

John John’s

temperature

occurrent

process

course of temperature

changes

John’s temperature history

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dependentcontinuant

quality

temperature

organism

John John’s

temperature

occurrent

process

life of an organism

John’s life

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BFO: The Very Top



dependentcontinuant

quality disposition

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BFO: The Very Top

continuant


dependentcontinuant

qualityfunctionroledisposition

occurrent

disposition- of a glass vase, to shatter if dropped- of a human, to eat - of a banana, to ripen- of John, to lose hair

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dispositionif it ceases to exist, then its bearer and/or its immediate surrounding environment is physically changedits realization occurs when its bearer is in some special physical circumstancesits realization is what it is in virtue of the bearer’s physical make-up

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function - of liver: to store glycogen- of birth canal: to enable transport- of eye: to see- of mitochondrion: to produce ATP

not optional; reflection of physical makeup of bearer

role optional:exists because the bearer is in some special natural, social, or institutional set of circumstances in which the bearer does not have to be

role - bearers can have more than one role

person as student and staff member- roles often form systems of mutual dependence

husband / wife first in queue / last in queuedoctor / patient

host / pathogen

role of some chemical compound: to serve as analyte in an experiment

of a dose of penicillin in this human child: to treat a disease

of this bacteria in a primary host: to cause infection


dependentcontinuant

function

to seeeye

John’s eye function of John’s eye: to see

occurrent

process

process of seeing

John seeing

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New York State Center of Excellence in Bioinformatics & Life Sciences

R T U New York State Center of Excellence in Bioinformatics & Life Sciences

R T U

Particulars and Universals

me this walking

my left leg

this leg moving

to makeme walk

human being

living creature

walkingleg moving

legfunction

process

Instance-of at t

Instance-of

Instance-ofat t

Instance-ofat t

Instance-of

1



R T U

instanceOf at t2 instanceOf at t1

instanceOf at t2

The importance of temporal indexing

#1’s stomach

benigntumor

instanceOf at t1

#4

malignanttumor

partOf at t1

stomach

partOf at t2



R T U

Continuants and Occurrents

me this walking

my left leg

this leg moving

to makeme walk

human being

living creature

walkingleg moving

legfunction

process

Instance-ofat t

Instance-of

Instance-ofat t

Instance-ofat t

Instance-of

2



R T U

Independent versus dependent

Independent entities

Do not require any other entity to exist to enable their own existence

Dependent entities

Require the existence of some other entity for their existence

me this walking

my left leg

this leg moving

to makeme walk

Independentcontinuants Dependent

continuantsOccurrents

(are all dependent)

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R T U

Dependent continuants

• Realized– Quality: redness (of blood)

• Realizable– Function: to flex (of knee joint)– Role: student– Power: boss– Disposition: brittleness (of a bone)

Realizations flexing

studying

ordering

breaking

continuants occurrents

3



R T U

Relation Ontology

ContinuantOccurrent

process, event

IndependentContinuant

~ thing

DependentContinuant

.... ..... .......

universals

particulars

has_participant

inheres_in instance_of (at t)

isa isa



R T U

t t tinstanceOf

The essential pieces

materialobject

spacetimeregion

mesome

temporal region

my life

my 4D STR

some spatialregion

coursespatialregion

temporalregion

dependent continuant

some quality

located-in at t

at t

participantOf at t occupies

projectsOn

projectsOn at t

OGMSOntology for General Medical

Science

http://code.google.com/p/ogms

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R T U

• 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

Ontology of General Medical Science (OGMS)



R T U

Motivation

• Clarity about:– disease etiology and progression

– disease and the diagnostic process

– phenotype and signs/symptoms

– entities in reality and observations of sucn entities

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Physical Disorder

:.

Physical Disorder

– independent continuantfiat object part

A causally linked combination of physical components of the extended organism that is clinically abnormal.

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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: baldness57

Big Picture

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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.

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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, enlarged spleen

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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 61

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.

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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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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


– 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


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).

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



Hypothesis - rule out Huntington’s suggests


Test results - molecular detection of the HTT gene with >39CAG repeats used_in


Result - diagnosis that patient X has a disorder that bears the disease Huntington’s disease

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

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


– recognized_as

• Symptoms - fatigue, anorexia

• Signs - jaundice, splenomegaly



Hypothesis - rule out cirrhosis suggests


Test results - elevated liver enzymes in serum used_in


Result - diagnosis that patient X has a disorder that bears the disease cirrhosis

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


– recognized_as

• Symptoms - headaches, dizziness

• Signs – elevated blood pressure



Hypothesis - rule out hypertension suggests


Test results - used_in


Result - diagnosis that patient X has a disorder that bears the disease hypertension

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



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


Result - diagnosis that patient X has a disorder that bears the disease type 2 diabetes mellitus

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



Hypothesis - suggests

Laboratory tests – produces

Test results – occasionally, skin testing used_in


Result - diagnosis that patient X has a disorder that bears the disease type 1 hypersensitivity to penicillin

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

John’s coronary heart disease

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asymptomatic (‘silent’) infarction

early lesions and small

fibrous plaques

stable angina

surface disruption of plaque

unstable angina

instantiates at t1

instantiates at t2

instantiates at t3

instantiates at t4

instantiates at t5

time


dependentcontinuant

disposition

diseasedisorder

John’s disordered

heart

John’s coronary heart

disease

occurrent

process

course of disease

course of John’s disease

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BFO and Ontology Design Principles Barry Smith 1.

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