The Vertebrate Bridging Ontology (VBO) Ravensara Travillian, James Malone, Chao Pang, John Hancock, Peter W.H. Holland, Paul Schofield, and Helen Parkinson

VBO project Goal: fill critical gap in data annotation—computational cross-species integration of data between key model vert organisms Most Recent Common Ancestor (MRCA) 2 VBO Zebrafish Anatomy Ontology Rat Anatomy Ontology Mouse Anatomy Ontology Mouse Subspecies Anatomy Ontologies Xenopus Ontology Human Anatomy Ontology

Use cases that homology enables Key questions evolutionary community may wish to ask: 1. Compare expression of (a) a named gene or (b) gene family or (c) combination of genes between species (query: which anatomical features? same/different? 2. Compare anatomical structure between species (query: same or different genes expressed?) 3. Test hypothesis of homology using gene expression similarity/difference between species? How to do so: view curated info through Atlas interface 3

Homology as basis for cross-species query 4

Clades, homology groupings, and MRCA/LCA 5

Homology mapping: top-down or bottom-up? Two theoretical approaches In practice, a hybrid approach, depending on evidence 6 MRCAHomology chaining Specified homology Inferred homology

Relations in VBO Relations defined in regard to homology 1. homologous-to: Example: chambers of mammalian heart; Indicative of evolutionary conservation 2.homologous-to some part-of: less specific, e.g. Tibia (Homo sapiens) and Fibula (Homo sapiens ) homo-logous- to some part-of Tibiofibula (Xenopus laevis ); Indicative of evolutionary event 3.not-homologous-to (for lexical matches): because of open- world assumption; Human frontal bone not-homologous-to zebrafish frontal bone 7

Homology relations: pairwise mappings 8 Structure Species in Structure Species in relation Source: GXA, MRC, EP Prove- nance

Pairwise mappings 9

Pairwise homology mappings Travillian: VBO workshop February

Mappings in Protégé Travillian: VBO workshop February

Homology: a maximally-connected graph Example: tetrapod acetabulum (concave surface on pelvis where femur meets) Symmetric Reflexive Transitive Maximally connected for homologous vertebrate structures Travillian: VBO workshop February

Limitations of Protégé in modelling homology Protégé cannot leverage subsumption to programmatically create maximally-connected graph Chao developed tool to create maximally-connected graph from pairwise mappings in spreadsheet Travillian: VBO workshop February

not-homologous-to: connected graph Travillian: VBO workshop February Mammalian acetabula Taenia saginata asiatica acetabulum Notomega- rhynchus navonae acetabulum

Multi-species interface Travillian: VBO workshop February

What can the user query from Atlas/VBO? Once VBO is integrated, user can ask: What structure in what species is homologous to what other structure in what other species? (validated and/or presumed) At what taxonomic level does this homology occcur (e.g., vertebrate, tetrapod, mammal) What lexically-matching structures are not actually homologous? What is the evidence for the claimed relationship? 7-8 February Travillian: VBO workshop 2

Thanks to: Tony Burdett, Tomasz Adamusiak, Onard Mejino, Melissa Haendel, Ann-Marie Mallon and Michael Gruenberger Jonathan Bard, Michael Ashburner, David Osumi- Sutherland Monte Westerfield, Terry Hayamizu, Hilmar Lapp, Paula Mabee, George Gkoutos Biotechnology and Biological Sciences Research Council (grant #BB/G022755/1)