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
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