A merger of multi-species anatomy ontologies
orAn 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
Vertebrata
Ascidians
Arthropoda
Annelida
Mollusca
Echinodermata
tetrapod limbs
ampullae
tube feet
parapodia
We want to understand gene function across taxa
Anatomy ontologies are used to describe morphological variation
Anatomy ontologies built for one species will not work for others
http://fme.biostr.washington.edu:8080/FME/index.html
http://ccm.ucdavis.edu/bcancercd/22/mouse_figure.html
lung
lung
lobular organ
parenchymatous organ
solid organ
pleural sac
thoracic cavity organ
thoracic cavity
abnormal lung morphology
abnormal respiratory system morphology
MPO
MA
FMA
abnormal pulmonary acinus morphology
abnormal pulmonary alveolus morphology
lungalveolus
organ system
respiratory system
Lower respiratory
tract
alveolar sac
pulmonary acinus
organ system
respiratory system
EHDAA2
lung
lung bud
respiratory primordium
pharyngeal region
develops_frompart_of
is_a (SubClassOf)
surrounded_by
So we build species-specific ontologies
lung
lung
lobular organ
parenchymatous organ
solid organ
pleural sac
thoracic cavity organ
thoracic cavity
abnormal lung morphology
abnormal respiratory system morphology
MPO
MA
FMA
abnormal pulmonary acinus morphology
abnormal pulmonary alveolus morphology
lungalveolus
organ system
respiratory system
Lower respiratory
tract
alveolar sac
pulmonary acinus
organ system
respiratory system
EHDAA2
lung
lung bud
respiratory primordium
pharyngeal region
But this results in silos
develops_frompart_of
is_a (SubClassOf)
surrounded_by
Why not just map ontology terms?Class A Class B Mapped? Useful?
FMA: extensor retinaculum of wrist
MouseAnatomy: retina Yes No
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
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?
Long ago in the world of anatomies
An anatomical reference ontology was built to help standardize species-specific ontologies
And then came Uberon, created to bridge model organism anatomies
anatomical structure
endoderm of forgut
lung bud
lung
respiration organ
organ
foregut
alveolus
alveolus of lung
organ part
FMA:lung
MA:lung
endoderm
GO: respiratory gaseous exchange
MA:lung alveolus
FMA: pulmonary
alveolus
is_a (taxon equivalent)
develops_frompart_of
is_a (SubClassOf)
capable_of
NCBITaxon: Mammalia
EHDAA:lung bud
only_in_taxon
pulmonary acinus
alveolar sac
lung primordium
swim bladder
respiratory primordium
NCBITaxon:Actinopterygii
Subsumption of species-specific classes
Mungall, C. J., Torniai, C., Gkoutos, G. V., Lewis, S. E., & Haendel, M. A. (2012). http://genomebiology.com/2012/13/1/R5
UBERON
cerebellum
cerebellarvermis
pp
cerebellum
cerebellar vermis
cerebellum
vermis of cereblleum
posterior lobe of
cerebellum
pp
MA:mouseFMA:human
GO/NIF: subcellular GO/NIF: subcellular
axon
CL:Purkinje cell
p
i i
CL:Purkinje cell
axon
i
ii
i
dendrite dendrite
cerebellum posterior
lobe
cerebellum posterior
lobe
p
pp
Uberon includes the
Cell Ontology to enable
query across granularity
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]
Fossils, the ultimate silo
Modern diversity only a fraction of evolutionary diversity
Missing evolutionary transitions e.g. fin to limb
Extant ontologies not always compatible with fossil data
Different data sources and resolution between extinct and extant
Shubin et al. 2006
And so over time…
… additional multi-species ontologies evolved
But…
…they had a hard time maintaining relationships to one another
And there was asynchrony in the universe
The big roll-up
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.obohttp://purl.obolibrary.org/obo/uberon/ext.owl
Example of ontology roll-up
Developmental Biology, Scott Gilbert, 6th ed.Fruit fly FBbt ‘tibia’ Human FMA ‘tibia’
UBERON: tibia
UBERON: bone
is_a
is_a
is_a
Vertebrata
Drosophila melanogaster
part_of
Homo sapiens
is_a
only_in_taxon
part_of
disjoint with
✗
Managing variation: using reasoners to detect errors
What can you do with the new uberon-ext?
Modified from Ahn and Ho 2008
Reason across anatomical variation in extinct and extant taxa Query for candidate genes relevant to morphological evolution
kb.phenoscape.org
Different strokes for different folksontology contents
basic simple relationshipshttp://purl.obolibrary.org/obo/uberon/basic.owl
uberon main ontologyhttp://purl.obolibrary.org/obo/uberon.owl
merged main ontology + links to GO, CL, NCBITaxon, NBOhttp://purl.obolibrary.org/obo/uberon/merged.owl
Composite-metazoan
Uberon plus species-specific ontology classes merged in http://purl.obolibrary.org/obo/uberon/composite-metazoan.owl
Uberon-ext Uberon merged plus TAO, AAO and VSAO terms merged inhttp://purl.obolibrary.org/obo/uberon/ext.owl
http://uberon.org Formats:
OBO-Format OWL
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!
Conclusions
Thanks!
Chris Mungall, Jim Balhoff, Frederic Bastian, David
Blackburn, Aurelie Comte , Wasila Dahdul , Alex Dececchi, Nizar Ibrahim, Suzi Lewis, Paula
Mabee, Anne Niknejad
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.