1 The OBO Foundry Towards Gold Standard Terminology Resources in the Biomedical Domain Thomas Bittner (based on a presentation by Barry Smith)

2 UMLS, Semantic Web, Moby, wikis, etc.  let a million flowers bloom  integration relies on post hoc mappings how create broad-coverage semantic annotation systems for biomedicine?

3 O1 O2 O4 O3 OnOn

4 O1 O4 O2 O3 OnOn

5 for science create an evolutionary path towards evidence-based terminology a new approach

6 O1 O2 O4 O3 OnOn

FMA RNAO ChEBI Cell Ontology PaTO Shared Organizatorial, Scientific, and Ontological principles TLO

8 for science create an evolutionary path towards evidence- based terminology Terminologies/ontologies that have proven their usefulness through applications based on/ verified through scientific methodology structured/formalized according to ontological principles a new approach

9 a shared portal for (so far) 58 ontologies originally called ‘GOBO’ (for Global Open Biological Ontologies) First step (Oct. 11, 2001)

10 GOBO Principles All ontologies will be welcome if, and only if, they conform to the following principles of gobo: 1. They are ‘open’ 2. They are in, or can be instantiated in, the GO syntax or extensions of this syntax. 3. They are orthogonal to other ontologies already lodged with gobo. 4. Shared ID space. 5. Terms are defined.

11 Second step (March 2004) Initiation by the Gene Ontology Consortium - logical reforms of the GO and related ontologies

12 e.g. linking GO logically to other OBO ontologies via cross-products id: CL: name: osteoblast def: "A bone-forming cell which secretes an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone." is_a: CL: relationship: develops_from CL: relationship: develops_from CL: GO Cell type (CL) New Definition + = Osteoblast differentiation: Processes whereby an osteoprogenitor cell or a cranial neural crest cell acquires the specialized features of an osteoblast, a bone-forming cell which secretes extracellular matrix.

13 The OBO Foundry further principles added + intense collaborative development Third step (2005-6)

14 a family of interoperable gold standard biomedical reference ontologies to serve the annotation of  scientific literature  model organism databases  clinical data à la Ida  experimental results  etc. The OBO Foundry

15 A prospective standard designed to guarantee interoperability of ontologies from the very start (contrast to: post hoc mapping à la UMLS) several ontologies now being constructed ab initio

16 Initial set of 10 principles = 5 GOBO principles (with broadened family of allowable types of syntax, including OWL- DL syntaxes) plus: 6. Collaborative development 7. Intelligible documentation. 8. Plurality of independent users. 9. Clearly specified content. 10. Uses relations which are formally defined

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 Mungallobo.sf.net/relationshiprelations 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 Consortiumwww.geneontology.org 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

CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Organism-Level Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) Cellular Process (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO) OBO Foundry coverage GRANULARITY RELATION TO TIME

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) Building out from the original GO

20 Current state of OBO Foundry 1. Ontologies already mature but still undergoing continuous reform: Cell Ontology (CL) Foundational Model of Anatomy (FMA) Gene Ontology (GO) Zebrafish Anatomy Ontology (ZAO)

21 2. Early versions exist Clinical Trial Ontology (CTO, part of OBI) Common Anatomy Reference Ontology (CARO, DB1 & DB2) Mosquito Anatomy Ontology (MAO) Ontology for Biomedical Investigations (OBI) Phenotypic Quality Ontology (PATO, DB1 & DB2) Protein Ontology (PRO) Relation Ontology (RO) RNA Ontology (RnaO)

22 3. Still in need of thorough review Chemical Entities of Biological Interest (ChEBI) Disease Ontology (DO) Sequence Ontology (SO) various other OBO ontologies (Mammalian Phenotype Ontology...)

23 4. Still in planning phase Biobank/Biorepository Ontology (BrO, part of OBI) Environment Ontology (EnvO) – inaugural meeting August, 2007 organized by NERC in OERC (Oxford E-Research Center) Fish Multi-Species Anatomy Ontology (funding received; no acronym yet) Infectious Disease Ontology (IDO) Mouse Adult Neurogenesis Ontology (MANGO) Xenopus Anatomy Ontology (XAO)

24 OBO Foundry Listservs (Jan. 2007)

25 Foundry developers have agreed in advance to accept a common set of principles designed to ensure  compatibility  interoperability  formal robustnesshttp://obofoundry.org/

26 CRITERIA  The ontology is open and available to be used by all.  The ontology is in, or can be instantiated in, a common formal language.  The developers of the ontology agree in advance to collaborate with developers of other OBO Foundry ontology where domains overlap. CRITERIA

27 CRITERIA  UPDATE: The developers of each ontology commit to its maintenance in light of scientific advance, and to soliciting community feedback for its improvement.  ORTHOGONALITY: They commit to ensuring that there is community convergence on a single controlled vocabulary for each domain

28 CRITERIA  IDENTIFIERS: The ontology possesses a unique identifier space within OBO.  VERSIONING: The ontology provider has procedures for identifying distinct successive versions.  The ontology includes textual definitions for all terms. CRITERIA

29  CLEARLY BOUNDED: The ontology has a clearly specified and clearly delineated content.  DOCUMENTATION: The ontology is well- documented.  USERS: The ontology has a plurality of independent users. CRITERIA

30  COMMON ARCHITECTURE: The ontology uses relations which are unambiguously defined following the pattern of definitions laid down in the OBO Relation Ontology.* * Smith et al., Genome Biology 2005, 6:R46 CRITERIA

31 The Foundational Model of Anatomy (FMA)

32 The Foundational Model of Anatomy (FMA) FMA Uni-Washington Protégé – frame system ngton.edu:8089/FM E/index.html Human anatomy

33 High level scheme Digital Anatomist Foundational Model of Anatomy (FMA) Mejino & Rosse, KR-Med 04 FMA= (At, ASA, ATA, Mk) where: At At = Anatomy taxonomy ASA ASA = Anatomical Structural Abstraction ATA ATA = Anatomical Transformation Abstraction Mk Mk = Metaknowledge

34 Anatomical Entity Physical Anatomical Entity Physical Anatomical Entity -is a- Non-physical Anatomical Entity Non-physical Anatomical Entity Anatomy Taxonomy ( Mejino & Rosse, KR-Med 04) Non-spatial entity (not located in space) Spatial entity (located in space)

35 Anatomical Entity Physical Anatomical Entity Physical Anatomical Entity -is a- Non-physical Anatomical Entity Non-physical Anatomical Entity Non-material Physical Anatomical Entity Non-material Physical Anatomical Entity Material Physical Anatomical Entity Material Physical Anatomical Entity Space Surface Line Anatomy Taxonomy ( Mejino & Rosse, KR-Med 04)

36 Anatomical spaces (is-a hierarchy)

37 Anatomical Entity Physical Anatomical Entity Physical Anatomical Entity -is a- Non-physical Anatomical Entity Non-physical Anatomical Entity Non-material Physical Anatomical Entity Non-material Physical Anatomical Entity Material Physical Anatomical Entity Material Physical Anatomical Entity Anatomical Structure Anatomical Structure Body Substance Body Substance Space Surface Line Anatomy Taxonomy ( Mejino & Rosse, KR-Med 04)

38 Anatomical Entity Physical Anatomical Entity Physical Anatomical Entity -is a- Non-physical Anatomical Entity Non-physical Anatomical Entity Non-material Physical Anatomical Entity Non-material Physical Anatomical Entity Material Physical Anatomical Entity Material Physical Anatomical Entity Anatomical Structure Anatomical Structure Body Substance Body Substance Biological Macromolecule Biological Macromolecule Acellular Anatomical Structure Acellular Anatomical Structure Cell Part Cell Part Cell Tissue Body Part Body Part Human Body Human Body Space Surface Line Organ System Organ System Organ Part Organ Part Anatomy Taxonomy ( Mejino & Rosse, KR-Med 04)

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

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