Biocuration presentation of Uberon anatomy ontology merge with TAO, VSAO, and AAO; and the history of anatomy ontologies.

1. A merger of multi-species anatomy
ontologies
or
An experiment in knowledge management
Biocuration 2013
Chris Mungall, Jim Balhoff, Frederic Bastian, David
Blackburn, Aurelie Comte , Wasila Dahdul , Alex
Dececchi, Nizar Ibrahim, Suzi Lewis, Paula Mabee,
Anne Niknejad, Melissa Haendel

2. We want to understand gene
function across taxa
Vertebrata
tetrapod limbs
Ascidians
ampullae
Echinodermata
tube feet
Arthropoda
Annelida
parapodia
Mollusca
Anatomy ontologies are used to describe morphological variation

3. Anatomy ontologies built for one
species will not work for others
http://ccm.ucdavis.edu/bcancercd/22/mouse_figure.html
http://fme.biostr.washington.edu:8080/FME/index.html

4. So we build species-specific ontologies
FMA
is_a (SubClassOf)
EHDAA2 part_of
develops_from
surrounded_by organ system solid organ
pharyngeal region
respiratory
primordium
respiratory parenchymatous
lung bud system organ
lung
MA Lower
thoracic respiratory lobular organ
organ system tract
cavity
MPO
abnormal respiratory thoracic respiratory
system morphology system
cavity organ
pleural sac lung
abnormal lung
morphology
lung
abnormal pulmonary
acinus morphology pulmonary
acinus
abnormal pulmonary lung
alveolus morphology
alveolar sac
alveolus

5. But this results in silos
FMA
is_a (SubClassOf)
EHDAA2 part_of
develops_from
surrounded_by organ system solid organ
pharyngeal region
respiratory
primordium
respiratory parenchymatous
lung bud system organ
lung
MA Lower
thoracic respiratory lobular organ
organ system tract
cavity
MPO
abnormal respiratory thoracic respiratory
system morphology system
cavity organ
pleural sac lung
abnormal lung
morphology
lung
abnormal pulmonary
acinus morphology pulmonary
acinus
abnormal pulmonary lung
alveolus morphology
alveolar sac
alveolus

6. Why not just map ontology terms?
Class A Class B Mapped? Useful?
FMA: extensor MouseAnatomy: retina Yes No
retinaculum of wrist
Vivo: legal decision Cognitive Atlas: decision Yes No
PlantOntology: Pith MouseAnatomy: medulla Yes No
TaxRank: domain NCI: protein domain Yes No
ZfishAnat: hypophysis MouseAnatomy: pituitary No Yes
TAO:fossa AdverseReactions: depression Yes No
FMA: colon GAZ: Colón, Panama Yes No
Quality: male Chebi: maleate 2(-) Yes No
String matching for mapping can lead to spurious results and
semantics of mappings and provenance are not always clear

7. Avoiding Silo-ization
Use ontologies that are:
 open
 documented
 reusable
 interoperable
 built according to shared principles
 reuse core relations and patterns
Problem:
How do we re-use in the presence of variability?

8. Long ago in the world of anatomies
CARO
FMA
EMAP EHDAA2
MA (mostly)
FBbt embryonic embryonic XAO ZFA
Adult adult
Drosophila mouse human Xenopus zebrafish
mouse human
An anatomical reference ontology was built to help standardize
species-specific ontologies

9. And then came Uberon, created to
bridge model organism anatomies
CARO
UBERON
FMA
EMAP EHDAA2
MA (mostly)
FBbt embryonic embryonic XAO ZFA
Adult adult
Drosophila mouse human Xenopus zebrafish
mouse human

10. Subsumption of species-specific classes
is_a (SubClassOf) anatomical
part_of structure
develops_from
capable_of
is_a (taxon equivalent) endoderm
only_in_taxon
organ part
foregut
swim bladder organ endoderm of
forgut
NCBITaxon:
respiration organ
Actinopterygii
respiratory
primordium
GO: respiratory
gaseous exchange
pulmonary acinus
alveolus lung lung primordium
NCBITaxon: Mammalia alveolus of lung alveolar sac lung bud
FMA:
pulmonary FMA:lung
MA:lung alveolus EHDAA:
MA:lung
alveolus lung bud
Mungall, C. J., Torniai, C., Gkoutos, G. V., Lewis, S. E., & Haendel, M. A. (2012). http://genomebiology.com/2012/13/1/R5

11. Uberon UBERON
includes the cerebellum
p p
Cell Ontology cerebellar cerebellum
i
to enable i
vermis posterior
lobe
query across i i
granularity cerebellum i i cerebellum
p p p pposterior
cerebellum
cerebellar vermis of lobe of
posterior
vermis cereblleum cerebellum
lobe
MA:mouse
p FMA:human p
dendrite dendrite
CL:Purkinje cell CL:Purkinje cell
axon axon
GO/NIF: subcellular GO/NIF: subcellular

12. Use of Uberon
 Annotation extensions GOA/UniProtKB [Chris’ talk]
 Construction of GO terms [Heiko's talk]
 Bgee cross-model homology-based expression search
[Frederic’s talk]
 Annotation of biospecimens from diverse taxa
[eagle-i.org]
 Phenotype similarity analyses to identify disease gene
candidates and models
 New project “Monarch Initiative” to build tools and
services for navigating phenotypes [see our poster
tonight]
 PhenoDigm analysis engine [Damian’s talk tomorrow]

13. Fossils, the ultimate silo
 Modern diversity only a fraction of
evolutionary diversity
 Missing evolutionary transitions e.g.
fin to limb
 Extant ontologies not always Shubin et al. 2006
compatible with fossil data
 Different data sources and resolution
between extinct and extant

14. And so over time…
CARO
UBERON
vHOG
Arthropod Vertebrate Homologous
Organs Group
HAO AAO TAO
Hymenoptera VSAO Amphibian Teleost
Vertebrate Skeletal
FMA
EMAP EHDAA2
MA (mostly)
FBbt embryonic embryonic XAO ZFA
Adult adult
Drosophila mouse human Xenopus zebrafish
mouse human
… additional multi-species ontologies evolved

15. But…
CARO
UBERON
vHOG
Arthropod Vertebrate Homologous
Organs Group
HAO AAO TAO
Hymenoptera VSAO Amphibian Teleost
Vertebrate Skeletal
FMA
EMAP EHDAA2
MA (mostly)
FBbt embryonic embryonic XAO ZFA
Adult adult
Drosophila mouse human Xenopus zebrafish
mouse human
…they had a hard time maintaining relationships
to one another

16. And there was asynchrony in the
universe

17. The big roll-up
CARO
UBERON-ext
Uberon
core
CL
Cell Ontology
VSAO AAO TAO
Vertebrate Skeletal Amphibian Teleost
FMA
EMAP EHDAA2
MA (mostly)
embryonic embryonic XAO ZFA
Adult adult
mouse human Xenopus zebrafish
mouse human

18. The new Uberon-ext
 Contents:
– Over 8,000 classes (terms), 2500+ added by Phenoscape
– Multiple relationships, including subclass, part-of and develops-
from
 Scope: metazoa (animals)
– Current focus is chordates
– Includes teleost, amniote, and amphibian specific classes
 Uberon classes are generic / species neutral
– ‘mammary gland’: you can use this class for any mammal!
– ‘lung’: you can use this class for any vertebrate (that has lungs)
http://purl.obolibrary.org/obo/uberon/ext.obo
http://purl.obolibrary.org/obo/uberon/ext.owl

19. Example of ontology roll-up

20. Managing variation: using reasoners
to detect errors
only_in_taxon
UBERON: bone Vertebrata
disjoint with 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’
Developmental Biology, Scott Gilbert, 6th ed.

21. What can you do with the new
uberon-ext?
kb.phenoscape.org
 Reason across anatomical variation in extinct and extant taxa
 Query for candidate genes relevant to morphological evolution
Modified from Ahn and Ho 2008

22. Different strokes for different folks
ontology contents
basic simple
relationshipshttp://purl.obolibrary.org/obo/uberon/basic.owl
uberon main ontology
http://purl.obolibrary.org/obo/uberon.owl
merged main ontology + links to GO, CL, NCBITaxon,
NBOhttp://purl.obolibrary.org/obo/uberon/merged.owl
Composite- Uberon plus species-specific ontology classes merged in
metazoan http://purl.obolibrary.org/obo/uberon/composite-metazoan.owl
Uberon-ext Uberon merged plus TAO, AAO and VSAO terms merged in
http://purl.obolibrary.org/obo/uberon/ext.owl
Formats:
http://uberon.org OBO-Format
OWL

23. Conclusions
 Model organism anatomies were difficult to query
across
 Uberon was developed to help integrate human and
model organism anatomy
 Uberon has been useful to align model organism
anatomy ontologies
 Palaeontolosts and evo-devo biologists needed
wider coverage
 A core set of vertebrate terms was needed by all
=> So we merged the ontologies, and now we can have
dinosaur bone data, model organism data, and human
data all integrated and queryable in one database!

24. Thanks!
Chris Mungall, Jim
Balhoff, Frederic Bastian, David
Blackburn, Aurelie Comte
, Wasila Dahdul , Alex
Dececchi, Nizar Ibrahim, Suzi
Lewis, Paula Mabee, Anne
Niknejad

25. Looking for a post-doc?
http://nescent.org/about/employment.php#PostDoc2
We are recruiting a postdoc with training in bioinformatics who is interested in studying
phenotypic evolution by combining model organism genetic data with comparative
anatomical data from throughout the vertebrates. Projects may range from primarily
computational to primarily biological.