Underlying Ontologies for Biomedical work - The Relation Ontology (RO) and Basic Formal Ontology (BFO) Thomas Bittner SUNY Buffalo Disclaimer: I recycle many slides originally made by Barry Smith

Overview Motivation BFO and RO Top-level categories and relations of BFO/RO Conclusions

Why do we need a top-level ontology such as Basic Formal Ontology (BFO) ?

Karen Eilbecksong.sf.net properties and features of nucleic sequences Sequence Ontology (SO) RNA Ontology Consortium(under development) three-dimensional RNA structures RNA Ontology (RnaO) Barry Smith, Chris Mungall obo.sf.net/relationship relations Relation Ontology (RO) Protein Ontology Consortium (under development) protein types and modifications Protein Ontology (PrO) Michael Ashburner, Suzanna Lewis, Georgios Gkoutos obo.sourceforge.net/cgi -bin/ detail.cgi? attribute_and_value qualities of biomedical entities Phenotypic Quality Ontology (PaTO) Gene Ontology Consortium cellular components, molecular functions, biological processes Gene Ontology (GO) FuGO Working Groupfugo.sf.net design, protocol, data instrumentation, and analysis Functional Genomics Investigation Ontology (FuGO) JLV Mejino Jr., Cornelius Rosse fma.biostr.washington. edu structure of the human body Foundational Model of Anatomy (FMA) Melissa Haendel, Terry Hayamizu, Cornelius Rosse, David Sutherland, (under development) anatomical structures in human and model organisms Common Anatomy Refer- ence Ontology (CARO) Paula Dematos, Rafael Alcantara ebi.ac.uk/chebimolecular entities Chemical Entities of Bio- logical Interest (ChEBI) Jonathan Bard, Michael Ashburner, Oliver Hofman obo.sourceforge.net/cgi- bin/detail.cgi?cell cell types from prokaryotes to mammals Cell Ontology (CL) CustodiansURLScopeOntology

Karen Eilbecksong.sf.net properties and features of nucleic sequences Sequence Ontology (SO) RNA Ontology Consortium (under development) three-dimensional RNA structures RNA Ontology (RnaO) Barry Smith, Chris Mungall obo.sf.net/relationship relations Relation Ontology (RO) Protein Ontology Consortium (under development) protein types and modifications Protein Ontology (PrO) Michael Ashburner, Suzanna Lewis, Georgios Gkoutos obo.sourceforge.net/cgi -bin/ detail.cgi? attribute_and_value qualities of biomedical entities Phenotypic Quality Ontology (PaTO) Gene Ontology Consortium cellular components, molecular functions, biological processes Gene Ontology (GO) FuGO Working Groupfugo.sf.net design, protocol, data instrumentation, and analysis Functional Genomics Investigation Ontology (FuGO) JLV Mejino Jr., Cornelius Rosse fma.biostr.washington. edu structure of the human body Foundational Model of Anatomy (FMA) Melissa Haendel, Terry Hayamizu, Cornelius Rosse, David Sutherland, (under development) anatomical structures in human and model organisms Common Anatomy Refer- ence Ontology (CARO) Paula Dematos, Rafael Alcantara ebi.ac.uk/chebimolecular entities Chemical Entities of Bio- logical Interest (ChEBI) Jonathan Bard, Michael Ashburner, Oliver Hofman obo.sourceforge.net/cgi- bin/detail.cgi?cell cell types from prokaryotes to mammals Cell Ontology (CL) CustodiansURLScopeOntology Many partly independent efforts

Domain ontologies organized according to formal ontological principles RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO)

Domain ontologies organized according to formal ontological principles RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO)

FMA Domain ontologies specify the semantics of the vocabulary of a particular domain: RNAO ChEBI Cell Ontology PaTO

FMA RNAO ChEBI Cell Ontology PaTO Top-level ontology TLO All domain ontologies use the same top level notions

FMA RNAO ChEBI Cell Ontology PaTO Top-level ontology BFO All domain ontologies use the same top level notions Ontological principles

FMA RNAO ChEBI Cell Ontology PaTO BFO All domain ontologies use the same top level notions Diversity in the specifics Commonality in the foundations

FMA RNAO ChEBI Cell Ontology PaTO BFO All domain ontologies use the same top level notions Facilitates interoperatibility

FMA RNAO ChEBI Cell Ontology PaTO BFO All domain ontologies use the same top level notions Facilitates interoperatibility

FMA RNAO ChEBI Cell Ontology PaTO All domain ontologies use the same top level notions Shared Organizational, Scientific, and Ontological principles RO

More acronyms: BFO vs. BFO-FOL vs. BFO-DL vs. RO

Kinds of Ontologies Terms General Logic Thesauri formal Taxonomies Frames (OKBC) Data Models (UML, STEP) Description Logics (DAML+OIL) Principled, informal hierarchies ad hoc Hierarchies (Yahoo!) structured Glossaries XML DTDs Data Dictionaries (EDI) ‘ordinary’ Glossaries XML Schema DB Schema Glossaries & Data Dictionaries MetaData, XML Schemas, & Data Models Formal Ontologies & Inference Thesauri, Taxonomies Michael Gruninger,

Ontologies: logical inferences Non-ontologies: no logical inferences Kinds of Ontologies Terms General Logic Thesauri formal Taxonomies Frames (OKBC) Data Models (UML, STEP) Description Logics (DAML+OIL) Principled, informal hierarchies ad hoc Hierarchies (Yahoo!) structured Glossaries XML DTDs Data Dictionaries (EDI) ‘ordinary’ Glossaries XML Schema DB Schema

Kinds of Ontology Languages General Logic Description Logics (DAML+OIL) Tradeoff between expressive power and computability How well can we specify intended meaning of terms What can we compute automatically

Kinds of Ontology Languages General Logic Description Logics (DAML+OIL) Tradeoff between expressive power and computability How well can we specify intended meaning of terms What can we compute automatically

Kinds of Ontology Languages General Logic Description Logics (DAML+OIL) Tradeoff between expressive power and computability How well can we specify intended meaning of terms What can we compute automatically

We need BOTH kinds of languages General Logic Description Logics (DAML+OIL) Tradeoff between expressive power and computability How well can we specify intended meaning What can we compute automatically

Computational representations of BFO

BFO-FOL ‘implementation’ of BFO in first order logic

Computational representations of BFO BFO-DL ‘implementation’ of BFO in the description logic OWL (Ontology WEB language) BFO-FOL ‘implementation’ of BFO in first order logic

Computational representations of BFO BFO-DL ‘implementation’ of BFO in OWL BFO-FOL ‘implementation’ of BFO in first order logic Focus on logically sound formulation of ontological principles high expressive power of FOL needed Focus on computation based on logically verified principles computational efficiency of a DL needed

26 BFO vs. RO RO = Relation ontology RO is a sub-set of BFO-DL that has been included in the OBO framework of ontologies

27 What is ‘in’ the Relation Ontology (RO) ??? Logically verified terminology that is relevant to the OBO-framework terminology for top-level categories terminology for top-level relations

Two distinct kinds of entities universalsparticulars typestokens classesinstances

Misha instances Tom Instance-of substance siamese Is-a cat Is-a mammal Is-a animal Is-a organism Is-a Human being Is-a Universals, classes, types

Particulars: Continuants vs. occurrents

Persistent entities

Continuant Persists through time in virtue of being wholly present at every time at which it exists at all. I exist in full at this moment in time

Persistent entities Continuant Persists through time in virtue of being wholly present at every time at which it exists at all. I exist in full at this moment in time Occurrent Evolve over time Do not exist in full at any given moment This presentation does not exist in full right now

Continuants have spatial parts

Occurrents (processes) have spatio-temporal parts t i m e process

Continuants do NOT have spatio- temporal parts I am a continuant The first 5-minute phase of my existence is not a spatio-temporal part of me It is a spatio-temporal part of my life My life is a process

Ontologies organized according to ontological principles RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO)

38 Kinds of continuants Independent continuants (substances) Dependent continuants

39 Kinds of continuants Independent continuants (substances) Dependent continuants

40 Kinds of continuants Independent continuants (substances) Dependent continuants

41 Kinds of continuants Independent continuants (substances) Dependent continuants the yellow color of this car the maximal speed of this car

42 Kinds of continuants Independent continuants (substances) Dependent continuants the mass of this planet its disposition to sustain life

43 Kinds of continuants Independent continuants (substances) Dependent continuants the mass of this molecule its disposition to engage in chemical reactions

Ontologies organized according to ontological principles RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO)

Ontologies organized according to ontological principles RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO)

Universals and particulars (cont.)

Misha substance instances Tom Instance-of substance siamese Is-a cat Is-a mammal Is-a animal Is-a organism Is-a Human being Is-a substance- Universals

Accidents: Species and instances quality color red scarlet R232, G54, B24 Barry Smith Universals among dependent continuants Is-a this individual token of redness (this token redness – here, now) Inst-Of

Of dependent continuants Universals and particulars Accidents: Species and instances substance animal mammal human Irishman this individual token man Of independent continuants

Substance universals Ontologies organized according to ontological principles RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO)

Quality/func tion universals Ontologies organized according to ontological principles RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO)

52 What is ‘in’ the Relation Ontology (RO) ??? Logically verified terminology that is relevant to the OBO-framework terminology for top-level categories terminology for top-level relations

53 What is ‘in’ the Relation Ontology (RO) ??? Logically verified terminology that is relevant to the OBO-framework terminology for top-level categories terminology for top-level relations

Misha instances Tom Instance-of substance siamese Is-a cat Is-a mammal Is-a animal Is-a organism Is-a Human being Is-a is-a relation between Unive rsals

Misha instances Tom Instance-of substance siamese Is-a cat Is-a mammal Is-a animal Is-a organism Is-a Human being Is-a is-a relation between Unive rsals Human Being is-a mammal Every instance of Human Being is also an instance of mammal

Misha instances Tom Instance-of hasPet isPetOf substance siamese Is-a cat Is-a mammal Is-a animal Is-a organism Is-a Human being Is-a is-a relation between Unive rsals IsPetOf

Instance-level relations universal-level relations Misha instances Tom Instance-of hasPet isPetOf cat Human being Universals HasPet IsPetOf

Universal parthood: Human anatomy The universal human body The universal human head Human heads are parts of human bodies

Universal parthood Human-heads Human-bodies Part-of

Universal parthood Human-heads Human-bodies HasPart

The semantics of universal parthood X PART-OF Y iff For every instance x of X there exists an instance y of Y such that x part-of y AND For every instance y of Y there exists an instance x of X such that x part-of y

General framework for defining universal-level relations in terms of relations between individuals R all-some (A, B) =: ∀ x (Inst(x, A) → ∃ y( Inst(y, B) & Rxy)) For every instance x of A there is some instance y of B such that R(x,y) holds R some-all (A, B) =: ∀ y (Inst(y, B) → ∃ x( Inst(x, A) & Rxy)) For every instance y of B there is some instance x of A such that R(x,y) holds R all-all (A, B) =: R all-some (A, B) & R some-all (A, B) R can be ANY binary relation

63 Important Individual-level relations

Independent Continuant Occurrent Dependent Continuant You, me, This molecule, My cat Misha Individual-level relations

Independent Continuant Occurrent Dependent Continuant My temperature (now) My height My role as a presenter Individual-level relations

Independent Continuant Occurrent Dependent Continuant Processes: My life, My presenting this talk Individual-level relations

Independent Continuant Occurrent Dependent Continuant Part-of My heart part-of my body Montana part-of United States Individual-level relations

Independent Continuant Occurrent ParticipatesIn Part-of the runner participates in the racing process the molecule participates in the diffusion process Dependent Continuant Individual-level relations

Dependent Continuant Independent Continuant Occurrent ParticipatesIn Part-of the racing involves racers the diffusion process involves molecules Involves Individual-level relations

Independent Continuant Occurrent Dependent Continuant ParticipatesIn Part-of the first 10 minutes of the presentation are part of the presentation my childhood is part of my life Involves Individual-level relations

Independent Continuant Occurrent Dependent Continuant ParticipatesIn RealizationOf PartOf The power of a catalytic RNA to catalyze a reaction is realized through a complex process of binding substrates in the correct orientation and stabilizing reaction intermediates The role of antibiotics in treating infections is realized via the killing of bacteria Involves Individual-level relations

Independent Continuant Occurrent Dependent Continuant ParticipatesIn RealizationOf PartOf A warming process yields a rise in temperature The tenure process yields a rise in John’s status Involves Changes quality Individual-level relations

Independent Continuant Occurrent Dependent Continuant ParticipatesIn InheresIn RealizationOf Part-of PartOf Your height inheres in you The role the antibiotics inheres in the antibiotics Involves Changes quality Individual-level relations

Independent Continuant Occurrent Dependent Continuant ParticipatesIn InheresIn RealizationOf Part-of PartOf Involves Changes quality Individual-level relations

Time-dependent relations ternary relations time as parameter R xyt the relation R holds between x and y and t My left hand is (individual) part of my left arm now Time-independent relations binary relations R xy the relation R holds between x and y Left Human Hand is part of Left Human Body (Canonical anatomy) Relations among independent persistent entities

76 Conclusions

FMA RNAO ChEBI Cell Ontology PaTO Based upon the top-level ontology BFO RO All domain ontologies use the same top level notions

Karen Eilbecksong.sf.net properties and features of nucleic sequences Sequence Ontology (SO) RNA Ontology Consortium(under development) three-dimensional RNA structures RNA Ontology (RnaO) Barry Smith, Chris Mungall obo.sf.net/relationship relations Relation Ontology (RO) Protein Ontology Consortium (under development) protein types and modifications Protein Ontology (PrO) Michael Ashburner, Suzanna Lewis, Georgios Gkoutos obo.sourceforge.net/cgi -bin/ detail.cgi? attribute_and_value qualities of biomedical entities Phenotypic Quality Ontology (PaTO) Gene Ontology Consortium cellular components, molecular functions, biological processes Gene Ontology (GO) FuGO Working Groupfugo.sf.net design, protocol, data instrumentation, and analysis Functional Genomics Investigation Ontology (FuGO) JLV Mejino Jr., Cornelius Rosse fma.biostr.washington. edu structure of the human body Foundational Model of Anatomy (FMA) Melissa Haendel, Terry Hayamizu, Cornelius Rosse, David Sutherland, (under development) anatomical structures in human and model organisms Common Anatomy Refer- ence Ontology (CARO) Paula Dematos, Rafael Alcantara ebi.ac.uk/chebimolecular entities Chemical Entities of Bio- logical Interest (ChEBI) Jonathan Bard, Michael Ashburner, Oliver Hofman obo.sourceforge.net/cgi- bin/detail.cgi?cell cell types from prokaryotes to mammals Cell Ontology (CL) CustodiansURLScopeOntology

Domain ontologies organized according to formal ontological principles RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO)