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.