Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara Travillian European Bioinformatics Institute

Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 9/10/10 2

Homology as basis for cross-species query Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 9/10/10 3

Biological use case Permit users to query annotations from large extant data store by homology (evolutionary relatedness) rather than analogy (similar function) Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 9/10/10 Anatomy Reference Ontology 4

What the user sees: entry portal 9/10/10 Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 5

What the user sees: genes and anatomy 9/10/10 Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 6

What the user sees: gene expression info 9/10/10 Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 7

Importance of anatomy in OBO ontologies Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 9/10/10 … (39 of others as of 16 Aug 2010) 8 ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔

Current mismatch: development, integration 9/10/10 Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian Most ontologies developed in order to meet species- specific need ZFIN (zebrafish) FlyBase (Drosophila) Various mouse databases And more… Specific focus makes integration across various ontologies difficult Therefore, potential has not yet been realised First step in process… 9

This study Compared anatomical terms in annotations from 3 diverse public multi-species datasets to entities in FMA and UBERON, 2 major anatomical ontologies Evaluated how well they matched as measure of how well they fit users’ needs Identified specific issues causing mismatches Made recommendations for better fit/bridging gap Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 9/10/1010

Methods Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 9/10/10 ZoomaOntology Mapper Exact matchingFuzzy matching (Metaphone/Double MP) AutomaticInteractive Searches many ontologiesSearches 1 ontology at a time Can discover mappings for new terms Can inherit mappings from elsewhereMaps everything de novo Open-source 2 tools x 2 ontologies 11

Methods 2 tools x 2 ontologies Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 9/10/10 FMAUBERON fma/release/index.html ERON:Main_Page Anatomy of canonical adult humanAnatomy of multiple species/stages Created to support medical anatomyCreated to facilitate comparison of phenotypes across multiple species >1,000,000 unique terms (8 June 2010)3936 unique terms (8 June 2010) 229 immediate matches277 immediate matches Few developmental termsIncludes developmental terms No process termsGO biological process terms No cross-species comparisons per seCross-species comparisons based on analogy rather than homology 12

Our data 22 species out of 700+ Annotations from 3 sources 1537 raw terms, 1311 normed Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 9/10/1013

Zooma output 9/10/10 Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 14

Ontology Mapper interactive output Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 9/10/1015

Results Very few exact string matches, so Zooma detected fewer matches than Ontology Mapper Zooma 286 matches in Uberon, 1025 unmatched 312 matches in FMA, 999 unmatched Ontology Mapper: 319 matches in Uberon, 992 unmatched 397 matches in FMA, 914 unmatched Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 9/10/1016

Results 9/10/10 Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 17

Precision and recall 9/10/10 Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 18

Conclusions Able to map the terms from the use cases to the ontologies Required a lot of effort and manual curation Precision and recall values indicate serious gaps We know which terms were available in which source We know which terms to concentrate on We know what is and what is not mapping and why We know what we want to suggest for FMA and Uberon 9/10/10 Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 19

Implications Why so few matches between such rich ontologies and real-life annotations? Uberon handles embryology and multiple species better; FMA more matches overall Issues with nonstandard usage by users Issues with terms and granularity in ontologies Implicit assumption of 1:1 and onto mappings in tools Need for bridge between ontologies: Vertebrate Bridging Ontology (VBO) Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 9/10/1020

Future work Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 9/10/10 Future work: using maps to make statemens about homologies based on literature, will be able to make querys based on homology for ev-deo use cases, which could not before. 21

Acknowledgements Functional Genomics Team: Helen Parkinson, James Malone Ontology Mapper: Tomasz Adamusiak Zooma: Tony Burdett Europhenome John Hancock, Ann-Marie Mallon ERA-PRO: Paul Schofield, Michael Gruenberger FMA Onard Mejino, Todd Detwiler UBERON: Melissa Haendel Funders: BBSRC, Gen2Phen, EMBL, Medical Research Council, EC’s FP6 Programme 9/10/10 Anatomy Ontologies & Potential Users: Bridging the Gap Ravensara S. Travillian 22