CoE Ontology Research Group (ORG) Barry Smith Center of Excellence in Bioinformatics and Life Sciences Ontology Research Group Department of Philosophy

u 2 Faculty and Staff Directors –Werner CeustersMedical School –Louis GoldbergDental School –Barry SmithPhilosophy Dept. Other researchers: –3 philosophers, 1 computer scientist, 1 business process analyst

u 3 Projects, funding & collaboration National Center for Biomedical Ontology ( Collaborating Center for Terminology under the auspices of the World Health Organisation (WHO) Advisory for the German national Electronic Health Record initiative Cleveland Clinic, Duke University

u 4

5 we need to know where in the body, where in the cell we need to know what kind of disease process = we need ontologies we need semantic annotation of data

u 6

7

8 Ontologies are systems of annotations

u 9 cellular locations molecular functions biological processes used to annotate the entities represented in the major biochemical databases thereby creating integration across these databases A set of standardized textual descriptions of

u 10 what cellular component? what molecular function? what biological process?

u 11 This process yields a slowly growing computer-interpretable map of biological reality within which major databases are automatically integrated in semantically searchable form

u 12 But also need to extend the methodology to other domains, including clinical medicine  need disease, symptom (phenotype) ontologies

u 13 the problem need for prospective standards to ensure mutual consistency and high quality of clinical counterparts of GO need to ensure consistency of the new clinical ontologies with the basic biomedical sciences if we do not start now, the problem will only get worse

u 14 the solution establish common rules governing best practices for creating ontologies and for using these in annotations apply these rules to create a complete suite of orthogonal interoperable biomedical reference ontologies

u 15 a shared portal for (so far) 58 ontologies (low regimentation)  NCBO BioPortal First step (2003)

u 16

u 17 Second step (2004): reform efforts initiated, e.g. linking GO to other OBO ontologies to ensure interoperability 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 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.

u 18 The OBO Foundry Third step (2006)

u 19 a family of interoperable gold standard biomedical reference ontologies to serve the annotation of  scientific literature  model organism databases  clinical data  experimental results The OBO Foundry

u 20 A prospective standard designed to guarantee interoperability of ontologies from the very start (contrast to: post hoc mapping) established March initial candidate OBO ontologies – focused primarily on basic science domains several being constructed ab initio now 16 ontologies

u 21 OntologyScopeURLCustodians Cell Ontology (CL) cell types from prokaryotes to mammals obo.sourceforge.net/cgi- bin/detail.cgi?cell Jonathan Bard, Michael Ashburner, Oliver Hofman Chemical Entities of Bio- logical Interest (ChEBI) molecular entitiesebi.ac.uk/chebi Paula Dematos, Rafael Alcantara Common Anatomy Refer- ence Ontology (CARO) anatomical structures in human and model organisms (under development) Melissa Haendel, Terry Hayamizu, Cornelius Rosse, David Sutherland, Foundational Model of Anatomy (FMA) structure of the human body fma.biostr.washington. edu JLV Mejino Jr., Cornelius Rosse Functional Genomics Investigation Ontology (FuGO) design, protocol, data instrumentation, and analysis fugo.sf.netFuGO Working Group Gene Ontology (GO) cellular components, molecular functions, biological processes Ontology Consortium Phenotypic Quality Ontology (PaTO) qualities of anatomical structures obo.sourceforge.net/cgi -bin/ detail.cgi? attribute_and_value Michael Ashburner, Suzanna Lewis, Georgios Gkoutos Protein Ontology (PrO) protein types and modifications (under development)Protein Ontology Consortium Relation Ontology (RO) relationsobo.sf.net/relationshipBarry Smith, Chris Mungall RNA Ontology (RnaO) three-dimensional RNA structures (under development)RNA Ontology Consortium Sequence Ontology (SO) properties and features of nucleic sequences song.sf.netKaren Eilbeck

u 22 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

u 23  Disease Ontology (DO) [SNOMED CT]  Biomedical Image Ontology (BIO)  Environment Ontology (EnvO)  Biobank Ontology (BrO)  Clinical Trial Ontology (CTO) [with WHO Global Trial Bank, Immune Tolerance Network, ACGT Advancing Genomics Clinical Trials in Cancer EU IP] Under construction

u 24 OBO low-regimentation ontology portal OBO Foundry high-regimentation collaborative initiative to create a gold standard suite of interoperable ontologies The vision

u 25  MICheck: ‘a common resource for minimum information checklists’ analogous to OBO / NCBO BioPortal  MICheck Foundry: will create ‘a suite of self- consistent, clearly bounded, orthogonal, integrable checklist modules’ * * Taylor CF, et al. Nature Biotech, in press The vision is spreading

u 26 Transcriptomics (MIAME Working Group) Proteomics (Proteomics Standards Initiative) Metabolomics (Metabolomics Standards Initiative) Genomics and Metagenomics (Genomic Standards Consortium) In Situ Hybridization and Immunohistochemistry (MISFISHIE) Phylogenetics (Phylogenetics Community) RNA Interference (RNAi Community) Toxicogenomics (Toxicogenomics WG) Environmental Genomics (Environmental Genomics WG) Nutrigenomics (Nutrigenomics WG) Flow Cytometry (Flow Cytometry Community) MICheck/Foundry communities

u 27 Current service offerings Analysis of data dictionairies, database schema’s and database models for ontological adequacy Curation of biomedical terminologies, ontologies and controlled vocabularies; Ontology creation, support in database merging and mapping Ontology support for clinical trials Ontology support for cross-disciplinary research collaborations