The document discusses the use of complex anatomical ontologies like Uberon in biocuration databases like Bgee. It notes that ontologies now include thousands of terms and complex relationships, making them difficult for curators to use. It describes how Bgee has simplified the use of Uberon by: 1) simplifying ontology relationships and removing redundant terms, 2) tracking annotation changes as the ontology updates, and 3) generating species-specific versions of Uberon to reduce complexity. Bgee is transferring all expression data annotations to Uberon and updating interfaces and data.

1. Use of Uberon in the Bgee database:
How to deal with a complex, large, dynamic
ontology?
Frederic Bastian
Biocuration 2013

2. A biocurator nightmare?
Ontologies now regularly include thousands of terms.
Complex relations are used, e.g., “transitively proximally
connected to”.
Curators are expected to provide complex annotations, e.g.:
post-composition of terms.
=> How can we simplify the use of complex ontologies?
© 2013 SIB

3. The Bgee database
http://bgee.unil.ch
© 2013 SIB

4. The Bgee database
http://bgee.unil.ch
Description of anatomy
and development
© 2013 SIB

5. The Bgee database
http://bgee.unil.ch
Expression data Description of anatomy
and development
© 2013 SIB

6. The Bgee database
http://bgee.unil.ch
Expression data Description of anatomy Homology
and development
© 2013 SIB

7. The Bgee database
…
http://tinyurl.com/bgee12-hoxa5a
© 2013 SIB

8. The Bgee database
…
http://tinyurl.com/bgee12-hoxa5a
© 2013 SIB

9. The Bgee database
…
http://tinyurl.com/bgee12-hoxa5a
© 2013 SIB

10. Use of anatomical ontologies in Bgee
Several species-specific ontologies were used:
• ZFA
• XAO
• FBbt
• EMAPA, MA
• EHDAA, EV
© 2013 SIB

11. Use of anatomical ontologies in Bgee
Several species-specific ontologies were used:
• ZFA
• XAO
• FBbt
• EMAPA, MA
• EHDAA, EV
=> Limitation to add new species
=> Inconsistent anatomical descriptions, different formalisms
adopted, etc.
© 2013 SIB

12. Homology relations between anatomical ontologies
To perform automated comparisons:
• We built groups of homologous organs
• We organized these groups into an ontology
VHOG:0000157 brain
EHDAA:2629 brain
EHDAA:300 brain
EHDAA:830 future brain
EMAPA:16089 future brain
EMAPA:16894 brain
EV:0100164 brain
MA:0000168 brain
XAO:0000010 brain
ZFA:0000008 brain
ZFA:0000146 presumptive brain
© 2013 SIB

13. Homology relations between anatomical ontologies
To perform automated comparisons:
• We built groups of homologous organs
• We organized these groups into an ontology
=> vHOG ontology
vHOG, a multispecies vertebrate ontology of homologous organs groups
Bioinformatics (2012) 28(7): 1017-1020, 2012.
© 2013 SIB

14. Homology relations between anatomical ontologies
To perform automated comparisons:
• We built groups of homologous organs
• We organized these groups into an ontology
=> vHOG ontology
To add a species:
• All groups need to be re-evaluated
• The graph structure needs to be updated
=> Not maintainable on the long run
© 2013 SIB

15. And then came Uberon …
only_in_taxon
UBERON: bone Vertebrata
is_a is_a
Drosophila melanogaster UBERON: tibia Homo sapiens
is_a is_a
part_of part_of
Fruit fly FBbt ‘tibia’ Human FMA ‘tibia’
© 2013 SIB

16. And then came Uberon …
only_in_taxon
UBERON: bone Vertebrata
is_a is_a
Drosophila melanogaster UBERON: tibia Homo sapiens
is_a is_a
part_of part_of
Fruit fly FBbt ‘tibia’ Human FMA ‘tibia’
© 2013 SIB

17. And then came Uberon …
Uberon also provides a composite ontology:
Merges terms from species-specific ontologies, when term
not present in Uberon.
....
is_a UBERON:0003059 ! presomitic mesoderm
devf UBERON:0002329 ! somite
is_a ZFA:0000073 ! somite 5 (zebrafish)
is_a ZFA:0000982 ! somite 6 (zebrafish)
is_a EHDAA2:0001853 ! somite 05 (embryonic human)
is_a EHDAA2:0001854 ! somite 06 (embryonic human)
=> Allow to import data from Model Organism Databases.
© 2013 SIB

18. And then came Uberon … BUT
Uberon is complex:
• About 22 000 terms in the composite ontology
© 2013 SIB

19. And then came Uberon … BUT
Uberon is complex:
• About 22 000 terms in the composite ontology
• Use of advanced constructs, supported only in OWL
• Use of high level abstract terms for interoperability
© 2013 SIB

20. And then came Uberon … BUT
Uberon is complex:
• About 22 000 terms in the composite ontology
• Use of advanced constructs, supported only in OWL
• Use of high level abstract terms for interoperability
• Frequently updated, highly responsive
• Structure changes when any imported species-specific
ontology changes => even more updated
© 2013 SIB

21. Uberon cannot be easily browsed
© 2013 SIB

22. First step: ontology simplification
© 2013 SIB

23. First step: ontology simplification
1. Simplification of the relations
Keep only is_a, part_of, develops_from.
Map all relations to their ancestors, e.g.:
develops_directly_from => develops_from
© 2013 SIB

24. First step: ontology simplification
2. Removal of redundant relations
A is_a B; B is_a C;
=> A is_a C is redundant.
© 2013 SIB

25. First step: ontology simplification
2. Removal of redundant relations
A is_a B; B is_a C;
=> A is_a C is redundant.
But, we consider part_of and is_a relations as equivalent.
A part_of B; B is_a C
=> A part_of C and A is_a C are considered redundant
This removes almost all “is_a anatomical entity”
© 2013 SIB

26. First step: ontology simplification
3. Removal of relations to upper_level terms
upper_level subset: "abstract upper-level terms not directly
useful for analysis”
Terms useful for analysis are almost all present under
“upper_level” terms, thus being confusing.
=> remove relations to “upper_level” terms if non-orphan
© 2013 SIB

27. First step: ontology simplification
3. Removal of relations to upper_level terms
upper_level subset: "abstract upper-level terms not directly
useful for analysis”
Terms useful for analysis are almost all present under
“upper_level” terms, thus being confusing.
=> remove relations to “upper_level” terms if non-orphan
[Term]
id: MA:0000747
name: lymph organ (mouse)
is_a: UBERON:0001062 ! anatomical entity
relationship: part_of UBERON:0002465 ! lymphoid system
© 2013 SIB

28. First step: ontology simplification
3. Removal of relations to upper_level terms
upper_level subset: "abstract upper-level terms not directly
useful for analysis”
Terms useful for analysis are almost all present under
“upper_level” terms, thus being confusing.
=> remove relations to “upper_level” terms if non-orphan
[Term]
id: MA:0000747
name: lymph organ (mouse)
is_a: UBERON:0001062 ! anatomical entity
relationship: part_of UBERON:0002465 ! lymphoid system
© 2013 SIB

29. First step: ontology simplification
3. Removal of relations to upper_level terms
upper_level subset: "abstract upper-level terms not directly
useful for analysis”
Terms useful for analysis are almost all present under
“upper_level” terms, thus being confusing.
=> remove relations to “upper_level” terms if non-orphan
[Term]
id: UBERON:0007502
name: epithelial plexus
is_a: UBERON:0000480 ! anatomical group
© 2013 SIB

30. First step: ontology simplification
4. Generate species-specific versions
To simplify even more the “composite-metazoan”
ontology, generate a version for each species used in
Bgee.
© 2013 SIB

31. First step: ontology simplification
© 2013 SIB

32. Second step: track ontology changes
1. Store annotation status
- “Perfect” annotation: would not need to be refined as
long as the term used is not obsoleted.
- “Missing granularity” annotation: a term is missing in the
ontology, e.g., vastus lateralis.
If a new child was added to the term, refine annotation
© 2013 SIB

33. Second step: track ontology changes
2. Track ontology changes
- Compare the versions used between two annotation
cycles.
- If a term used in a “missing granularity” annotation has
new children, refine the annotation.
© 2013 SIB

34. Conclusion 1/2
To manage complex, frequently updated ontology:
1. Provide a formal version for the reasoning, and a
simplified view for the end-user.
2. Store annotation status, to focus only on annotations
which need to be updated.
© 2013 SIB

35. Conclusion 2/2
Major update of Bgee incoming for fall 2013:
- All expression data annotations are being transferred to
Uberon.
- All homology information are being transferred from
vHOG to Uberon, using an external file.
© 2013 SIB

36. Conclusion 2/2
Major update of Bgee incoming for fall 2013:
- All expression data annotations are being transferred to
Uberon.
- All homology information are being transferred from
vHOG to Uberon, using an external file.
And also:
- Besides present/absent calls, Bgee will include:
overexpression calls; biologically significant expression.
- Revamped interfaces, webservices, APIs, …
© 2013 SIB

37. Advertisement! Other Bgee-related work
Poster 145:
Average rank IQR: a new improved method for
Affymetrix microarray quality control for meta-
analyses and database curation.
Marta Rosikiewicz
Database biocuration virtual issue:
Uncovering hidden duplicated content in public transcriptomics
data
Marta Rosikiewicz, Aurélie Comte, Anne Niknejad, Marc Robinson-
Rechavi, and Frederic B. Bastian
Database Vol. 2013, bat010; doi:10.1093/database/bat010
© 2013 SIB

38. Thank You
Aurélie Comte Sébastien Moretti Anne Niknejad Marta Rosikiewicz
Marc Robinson-Rechavi Komal Sanjeev Mathieu Seppey
And also:
• Melissa Haendel
• Chris Mungall