Uberon – an integrative multi-species anatomy ontology

Chris Mungall, Lawrence Berkeley LaboratoryMonarch InitiativeGene Ontology ConsortiumPhenoscape

EBI Industry Workshop 2013

What is an anatomical ontology?

Anatomical data annotation

Uses of anatomical ontologies

• Transcriptome data– Genes expressed in hippocampal CA1 region

• Describing clinical phenotypes– Loss of beta cells in the pancreas

• Biospecimen annotation– Liver-derived sample

• Functional characterization of gene products– BMP4 involved in bone development

• Describing species diversity– Extant avians lack teeth but have feathers

• NLP and text processing

More than a terminology

• Use of is-a (Sub Class Of)– Tell me about phenotypes that affect

bone growth• Answers include femur growth phenotypes

• Use of part-of–Which genes are expressed in the

hippocampus• Answers include genes expressed in CA1

region

Use of relationships in anatomical ontologies

• Use of develops-from– Cancers of neural-crest lineage cells?

• Answers include melanocytomas

• Use of other relationship types– Structures are made from connective

tissue?– Branches of the trigeminal nerve?– Brain regions associated with ataxia?– Neurons that secrete dopamine?– Brain regions near the striatum?

Which ontology?

• Mouse:– MA (adult)– EMAP (embryo, staged)– EMAPA (embryo,

abstract)

• Other models– XAO - Xenopus– ZFA – zebrafish– FBbt – Drosophila– WBbt – C elegans– DDAnat – Dictyostelium– …

• Human– FMA (adult)– EHDAA2 (CS1-

CS20)– SNOMED-CT– NIF GrossAnatomy

(mammal brain)– …

Which ontology?

• Mouse:– MA (adult)– EMAP (embryo, staged)– EMAPA (embryo,

abstract)

• Other models– XAO - Xenopus– ZFA – zebrafish– FBbt – Drosophila– WBbt – C elegans– DDAnat - Dictyostelium

• Human– FMA (adult)– EHDAA2 (CS1-

CS20)– SNOMED-CT– NIF GrossAnatomy– …

Why not just select one and adopt it as the

standard?

Why not just pick one?

http://fme.biostr.washington.edu:8080/FME/index.html

FMA

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

x

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

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

Ontologies built for one species will not work for others

http://en.wikipedia.org/wiki/Pharyngeal_jaw

Can we effectively apply model organism data to human?

Washington, N. L., Haendel, M. A., Mungall, C. J., Ashburner, M., Westerfield, M., & Lewis, S. E. (2009). Linking Human Diseases to Animal Models Using Ontology-Based Phenotype Annotation. PLoS Biol, 7(11). doi:10.1371/journal.pbio.1000247

lung

lung

respiratory gaseous exchange

lobular organ

parenchymatous organ

solid organ

pleural sac

thoracic cavity organ

thoracic cavity

multicellular organismal process

abnormal lung morphology

abnormal respiratory system morphology

GO

MPO

MA

FMA

abnormal pulmonary acinus morphology

abnormal pulmonary alveolus morphology

lungalveolus

respiratory system process

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

The problem: Data Silos

lung

lung

respiratory gaseous exchange

lobular organ

parenchymatous organ

solid organ

pleural sac

thoracic cavity organ

thoracic cavity

multicellular organismal process

abnormal lung morphology

abnormal respiratory system morphology

GO

MPO

MA

FMA

abnormal pulmonary acinus morphology

abnormal pulmonary alveolus morphology

lungalveolus

respiratory system process

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

Can we map between terms?

Automated mapping doesn’t workClass A Class B In mapping DB? Useful?

FMA extensor retinaculum of wrist

MA retina Yes No

FMA portion of blood MA blood No Yes

ZFA Macula MA macula Yes No

ZFA aortic arch MA arch of aorta Yes Misleading

ZFA hypophysis MA pitiuitary No Yes

FMA tibia FBbt tibia Yes No

FMA colon GAZ Colón, Panama Yes No

Linking animal models to human disease through a multi-species anatomy ontology

• Initial Approach:– Generalize existing species-specific

anatomy ontology terms– Use these as a bridge to connect data

Mungall, C. J., Torniai, C., Gkoutos, G. V., Lewis, S. E., & Haendel, M. A. (2012). Uberon, an integrative multi-species anatomy ontology. Genome Biology, 13(1), R5. doi:10.1186/gb-2012-13-1-r5 http://genomebiology.com/2012/13/1/R5

lung

FMA:lungMA:lung

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

Uberon: a multi-species anatomy ontology

• Contents:– 11,000 classes (terms)–Multiple relationship types, including

subclass (is-a), part-of and develops-from

– Detailed OWL axiomatization

• Scope: metazoa (animals)– Current focus is chordates

• Particularl emphasis on mammalia

– Federated approach for other taxa

Text processing• Sync with other

ontologies

Manual CurationLiteratureWorkshops with domain expertsTracker

OWL Reasoning• Auto-classification• QC pipeline

Uberon iterative development cycle

2009:Primarily entity-matching basedontology

2013:Almost entirely manual curation and automated reasoning

Uberon for NLP and text mining

• Lexical contents– 11414 primary labels– 29753 synonyms• Classified by category (broad, narrow, exact,

related)• Tagged with source• Additional synonym types (abbreviations,

formal Latin term, plural, etc)

– 270 adjectival forms• E.g. “hippocampal”

Uberon as a bridge between anatomy ontologies

• Cross-references to– FMA (4627)– Human developmental anatomy [Bard et al] (1463)– Multiple model organism anatomy ontologies (15256)

• MA, ZFA, etc

– Allen Brain Atlas (273)– NIF Neuroanatomical Ontology (1013)– SNOMED-CT (3453)– UMLS (2189)– NCI thesaurus (2286)– Wikipedia/Dbpedia (2966)– EFO (616)– …

• Cross-references are curated and validated– Manually– Through OWL reasoning

Bridging orthogonal resources

• Validated logical relationships connecting– Cell types (OBO Cell Ontology, CL)– Taxonomy (NCBI)– Functional and developmental

knowledge (GO)– Behaviors (NBO)– Proteins (PRO)– Chemical entities (CHEBI)

UBERON: trachea

UBERON:respiratory airway

CL: tracheal epithelial cell

CL: epithelial cell

is_a

part_of

is_a

NCBITaxon:Vertebrata

only_in_taxon

UBERON: respiratory system

part_of

GO:respiratory gaseousexchange

capable_of

Multi-ontology knowledge graph

MA:blood vessel

UBERON: retinal blood vessel

MP:abnormal retinal blood vessel morphology

Phenotype of

is_a

MA: retina

HP: Central retinal artery vascular tortuosity

FMA:central retinal artery

Phenotype of

Connecting phenotype ontologies through anatomy

Uberon on the semantic web

Permanent URL

Humans see HTML view

Integrated views in Monarch

http://monarchinitiative.org

Linking model systems tohuman diseases

Challenge: building the right view

• An ontology built for multiple purposes will usually be more complex than one built for one purpose– Most people don’t need the whole ontology

• Solution: create subsets or views– Based on

• Taxonomy (e.g. mouse plus human)• Organ system (e.g. skeletal)• Domain (e.g. diabetes)

– See• http://uberon.org

Challenge: visualization

http://ols.wordvis.com/q=UBERON:0002107

Latest developments

• Evolution of ontology– Initial goals: primarily a mapping resource– Now: Data is being annotated to Uberon directly

• Gene expression, transcriptomic, phenotype, functional

• The big roll up– Community converging around a single solution– Multiple ontologies being absorbed

• Anatomy subset of EFO• Neuro-Anatomy subset of NIFSTD• CALOHA (NextProt)• vHOG (Bgee gene expression db)• VSAO (Evolutionary biologists)

Availability

• Web page:– http://uberon.org– Multiple different OWL and Obo-format views available

• Browsing:– http://www.ontobee.org/browser/index.php?o=

UBERON– http://amigo2.berkeleybop.org/– http://ols.wordvis.com/ont=UBERON

• Tracker:– http://purl.obolibrary.org/obo/uberon/tracker

• Mailing list– https://lists.sourceforge.net/lists/listinfo/obo-anatomy

Summary

• Multiplicity of ontologies causes problems– Duplication of effort– Data silos

• Uberon bridges across species-specific anatomical ontologies– Can function as a standalone vertebrate anatomy

ontology

• A common multi-species anatomy ontology can bridge multiple datatypes– Gene expression– Phenotype– …

AcknowledgmentsUberon Developers• Alex Dececchi• Nizar Ibrahim• Wasila Dahdul• Melissa

Haendel

Contributors• Carlo Torniai (eagle i)• George Gkoutos (NBO)• Jonathan Bard

(EHDAA2)• Terry Meehan (CL)• Alex Diehl (CL)• Terry Hayamizu (MA/CL)• Yvonne Bradford (ZFA)• Ceri van Slyke (ZFA)• David Hill (GO)• David Osumi Sutherland

(FBbt/CARO)• Paul Schofield (MPATH)• Wasilla Dahdul

(TAO/VSAO)

Applications and software development• Frederic Bastian• Heiko Dietze• Jim Balhoff• Paula Mabee• Suzanna Lewis

Contributors• Erik Segerdell (XAO /

Phenotype RCN)• Paul Sereno (Phenoscape)• Monte Westerfield (ZFA)• Cynthia Smith (MP)• Maryanne Martone (NIF)• Bill Bug (NIF)• Aurelie Comte (Bgee)• Anna Niknejad (Bgee)• Marc Robinson-Rechavi

(Bgee)• Robert Druzinsky (FEED)• Brian K Hall (neural crest)• Sarah Whitcher Kansa• Ann Maglia (AAO)• Paul Sereno (Phenoscape)• David Blackburn

(Phenoscape)

Different versions for different purposes

ontology contents

basic simple relationships

http://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, NBO

http://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 http://uberon.org

Formats: • OBO-Format • OWL

Bridging anatomy ontologies

ZFA

MA FMA

EHDAA2

EMAPA

Uberon

CJ Mungall, C Torniai, GV Gkoutos, SE Lewis, MA Haendel.Uberon, an integrative multi-species anatomy ontology. Genome biology 13 (1), R5

SNOMED

NCIt