1. May 30, 2005BIONLP Lexical Issues in Anatomical Ontologies Sarah Luger www.xspan.org based on work with Stuart Aitken and Bonnie Webber

2. May 30, 2005BIONLP XSPAN Objectives To support access to tissue-based genetic information that is indexed by anatomy across species, via anatomy ontology integration. –homology relationships –function similarities –lineage relationships –cell types

3. May 30, 2005BIONLP A Mapping Problem Mouse Tail

4. May 30, 2005BIONLP A Mapping Problem C. Elegans Tail Mouse tail to C. elegans tail Same name, different function

5. May 30, 2005BIONLP A Mapping Problem In mouse: embryo/ organ system/ sensory organ/ eye/ optic stalk/ optic nerve In drosophila: larva/ larval organ system/ larval nervous system/ larval central nervous system/ larval brain/ medulla anlage/ optic nerve Mouse optic nerve to drosophila optic nerve –Same name, same function –The ontologies show different paths.

6. May 30, 2005BIONLP A Mapping Problem Identify and exploit relationships between tissues across the key model organisms given: –Mouse: 3559 anatomical parts –Drosophila: 506 anatomical parts –C. Elegans: 242 anatomical parts –Zebrafish: ~1200 anatomical parts –Human: 2328 anatomical parts Can their terminologies and anatomical ontogolies suggest what parts may be similar (homologous)?

7. May 30, 2005BIONLP Lexical Analysis Language processing: normalize, remove stop words, stemmed and lemmatized and then treated as unordered set Use more than the leaf label –Context, terms are not unique –Important terms spread across path The last term is weighted more than all prior terms combined. This filters out some “garbage” when comparing similar root-to-leaf paths with vastly different levels of specificity.

8. May 30, 2005BIONLP Weighting Example EMAPA.18237: Mouse/ embryo/ organ system/ sensory organ/ eye/ lens/ capsule 0 1 2 4 8 16 32 EHDAA.9045: 100% match Human/ embryo/ organ system/ sensory organ/ eye/ lens/ capsule 0 1 2 4 8 16 32 EHDAA.4727: 87% similar or 55/63 Human/ embryo/ organ system/ sensory organ/ eye/ lens vesicle/capsule 0 1 2 4 8 8 32

9. May 30, 2005BIONLP Weighting Example 1.EHDAA.9045: Human/ embryo/ organ system/ sensory organ/ eye/ lens/ capsule 2.EMAPA.18979: Mouse/ embryo/ organ system/ visceral organ/ reproductive system/ female/ ovary/ capsule 3.EMAPA.18679: Mouse/ embryo/ organ system/ visceral organ/ renal urinary system/ metanepheros/ excretory component/ cortex/ capsule

10. May 30, 2005BIONLP Methodology Use a similarity threshold to limit the number of results. Resultant pairs have one to many mappings: EMAPA: 18237EHDAA.9045 EMAPA: 18237 EHDAA.4727 Tissue pairs then structurally assessed by taking the ontologies as graphs with directed but unlabeled edges. –Examine intra-species relationships –Check relative positions of the terms between species –Judge comparisons as contradictory, supported, or no evidence.

11. May 30, 2005BIONLP Mouse-Human Results Threshold Matched Pairs Support 100%1223 90.4% 96% 1763 84.7% 94% 3037 92.8% This improvement follows from the larger set of lexical matches having more common terms near the top of the ontology, which permits paths that were previously being rejected.

12. May 30, 2005BIONLP Mouse-Human Results Mappings between human and mouse terms, where the x-axis represents thresholds of lexical similarity.

13. May 30, 2005BIONLP Human-Drosophila Results Fewer matches so we chose lexical similarity levels of 75%, 66% and 50%. Some contradictory mappings appear at 50%. The proportion of compatible mappings drops as the comparison threshold is reduced. An increase in mapping score is again observed.

14. May 30, 2005BIONLP Future Work Different name, same function –Introduces the need for synonym tables. Working with an anatomist to include synonyms in the mouse anatomy. –Zebrafish is also working on this. Discover more differences in ontology terms and free-text terms.

15. May 30, 2005BIONLP Ontologies, Mapping and Synonyms drosophila isa whole organism part of organ system isa reproductive system isa male reproductive system part of testis C. elegans part of organ system isa sex-associated system isa male-associated system isa male reproductive system isa male gonad gonad testis

16. May 30, 2005BIONLP COBrA: Ontology Mapping

17. May 30, 2005BIONLP COBrA: A GO editor hyperlink GO term data search

18. May 30, 2005BIONLP COBrA: A GO editor

19. May 30, 2005BIONLP Structural Analysis