1. The “über-ontology” (Uberon) Melissa Häendel, Chris Müngall, George Gkoütos Cell Ontology Workshop May, 2010

2. Uberon consists of species-neutral classes derived from many contributing ontologies What is Uberon? UBERON: ear vesicle UBERON: ear vesicle D

3. Uberon composition Uberon classes subsume classes in contributing AOs 13629 Xrefs to 4087 classes

4. Anatomical ontology domains and Uberon CARO TAOAAO XAOZFA UBERON MAFBbt

5. Uberon advantages Logical definitions in species-neutral ontologies Ontology alignment Mapping validation Reasoning across species Homology neutral

6. Logical definitions in GO using Uberon Uberon can make explicit many anatomical definitions already in GO GO:notochord formation: The formation of the notochord from the chordamesoderm. The notochord is composed of large cells packed within a firm connective tissue sheath and is found in all chordates at the ventral surface of the neural tube. In vertebrates, the notochord contributes to the vertebral column.

7. Logical definitions in CL using Uberon UBERON: trachea UBERON: respiratory airway CL: tracheal epithelial cell CL: epithelial cell is_a part_of is_a Vertebrata only_in_taxon Uberon trachea: A trachea held open by up to 20 C-shaped rings of cartilage. The trachea is the portion of the airway that attaches to the bronchi as it branches. [GO:0060438, Wikipedia:Vertebrate_trachea] Uberon can help ensure applicability of definitions in CL that rely on gross anatomical structures.

8. Uberon logical definitions represent functional, developmental, spatial, etc., axes of classification Logical definitions in Uberon using external ontologies UBERON: trachea UBERON: respiratory airway CL: tracheal epithelial cell CL: epithelial cell is_a part_of is_a Vertebrata only_in_taxon UBERON: respiratory system part_of GO: respiratory gaseous exchange capable_of

9. Differences in bone and bone tissue representation Ontology alignment

10. Using Uberon for alignment facilitates identification of missing classes Ontology alignment

11. Using Uberon to validate ontology mappings Class AClass BBiportalUberon FMA portion of bloodMA bloodNoYes ZFA MaculaMA maculaYesNo ZFA aortic archMA arch of aortaYesNo ZFA hypophysisMA pitiuitaryNoYes FMA gustatory organFBbt gustatory sensory organ NoYes FMA extensor retinaculum of wrist MA retinaYesNo FMA tibiaFBbt tibiaYesNo Many of these mappings have higher level least-common subsumers

12. Developmental Biology, Scott Gilbert, 6 th ed. Using Uberon to validate ontology mappings Text match mapping Fruit fly ‘tibia’Human ‘tibia’ UBERON: tibia UBERON: bone is_a Vertebrata Drosophila melanogaster part_of Homo sapiens is_a only_in_taxon part_of NOT is_a

13. Text matching Stem and synonym matching Curation Remove or split classes that are not biologically similar Reasoning Keep axioms that are consistent across AOs automated consistency checks for disjointeness violations Uberon iterative development cycle

14. Reasoning across species: querying for genes in similar structures Genetic mechanisms may be reused in analogous structures Structures may be homologous in ways that are yet undetermined Vertebrate chambered heart Arthropod dorsal vessel Xavier-Neto et al., Cell Mol Life Sci, 2007 Process Conserved genes Specification tinman/nkx2.5, wnts A-P patterning Hox genes, RA Morphogenesis Seven-up/Couptf-II Uberon heart: A hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood. [GO:0007507] Xrefs to FBbt, ZFA, FMA, etc. Uberon has a heart.

15. Panganiban et al., PNAS, 1997 Distal-less orthologs participate in distal-proximal pattern formation and appendage morphogenesis Distal-less (Dll) expression mouse limb sea urchin tube feet ascidian ampulla polychaete parapodia Reasoning across species: querying for genes in similar structures

16. What about homology? Evolutionary community: Capture multiple homologous_to statements external to Uberon using evidence and attribution. Allows for phylogenetic optimization. Model organism databases: Use single well-established homologous_to relations between structures in different MODs to create homology links between structures. ZFIN Uberon is homology-neutral

17. Uberon Conclusions Species-neutral ontology that subsumes contributing taxon-specific anatomy ontologies Useful for ontology alignment Useful for mapping validation Can be used for logical definitions in other species- neutral OBO ontologies Inferred multiple inheritance to represent non- structural axes of anatomical classification Allows query across species for similar structures and separate homology attribution

18. http://github.com/cmungall/uberon Uberon is available at: http://obofoundry.org/wiki/index.php/UBERON:Main_Page More information is here: (open uberon_edit.obo with the reasoner on)