integrating phenotype ontologies across multiple species

Integrating phenotype ontologies across multiple species

Caltech 2009

Chris Mungall

Conservation of phenotypes

How do we compare phenotypes across species?

Multiple project or species specific phenotype ontologies

• MP: mouse• HP: human• WP: worm• TO: plant• APO: fungi

– Data is not comparable– How do we know they are built according to the

same principles?

Anatomical and structural entities in OBO

MP MP-is_a hierarchy-hand-crafted

PATO EQ Descriptions

• PATO:– ontology of qualities

• EQ Descriptions– An expression consisting of:• a PATO ID (Q)• A bearer entity (E)• Optional additional tags

Examples

Relational Qualities

Have a bearer - have an additional dependency on some type of entity

EQ expressions can be written in obo format

Why?Formal semanticsEdit within OBO-Edit as genus-differentia definitionsUse the OBO-Edit reasoner

Can also be translated to OWL

EQ expressions can be written in obo format

Why?Formal semanticsEdit within OBO-Edit as genus-differentia definitionsUse the OBO-Edit reasoner

Can also be translated to OWL

EQ OBO

E=<E>Q=<Q>

intersection_of: <Q>intersection_of: inheres_in <E>

E=<E>Q=<Q>E2=<E2>

intersection_of: <Q>intersection_of: inheres_in <E>intersection_of: towards <E2>

EQ expressions can be written in obo format

EQ OBO

E=Femur MA:0001359 Q=decreased diameter PATO:0001715

intersection_of: PATO:0001715 intersection_of: inheres_in MA:0001359

E=Spleen MA:0000141 Q=concentration of PATO:0000033 E2=iron CHEBI:18248

intersection_of: PATO:0000033 intersection_of: inheres_in MA:0000141 intersection_of: towards PATO:0000033

EQ vs dedicated phenotype ontology

• Some groups pre-compose phenotype descriptions– terms generated in advance by ontology editor– ontology editors adds defs etc– dedicated phenotype ontology

• often species-specific

• Other groups post-compose phenotype descriptions– descriptions composed as needed by annotators– no dedicated phenotype ontology

Methodologies

Unifying descriptions

Equivalence MappingsbetweentermEQ expression

Methods

• Use obol to generate first pass and updates– parses term name– assumes semi-controlled syntax

• Manually edit obo xp file

Results

Advantages

• Reuse PATO across ontologies– Make sure we’re saying the same thing

• We can use the OBO-Edit reasoner to compute the is_a hierarchy

• We can enhance queries within species.– E.g. find all genes that have a phenotype affecting

sperm (CL:0000019 / WBbt:0006798)• We can compare across species

Reasoning

Reasoner Results: HP/MP

Comparing across species

• Requirements:– Phenotype ontology mappings– Mappings between anatomy ontologies

• Uberon– Multi-species anatomy ontology– No assumption of homology

• Analogy is useful to; e.g. eyes

– Scope: metazoans– Applicability outside vertebrates controversial

• Better to focus on cells (CL)

Mapping AOs to Uberon

Phenoblast: Quantifying similarity

SimJ: 0.42MaxIC: 13.4

SimJ: 0.32MaxIC: 12.1

SimJ: 0.17MaxIC: 6.2

Recoveringpathwaymembersby phenotypicsimilarity

Conclusions

• Sharing ontologies is good• PATO / EQs can be used to help build ontologies as

well as in annotation– Find mistakes– Automatically build DAG (reasoning)

• Mapping a phenotype ontology to EQs gives you the best of both worlds– Control over the terms used in annotation– Comparing data across species

• Where anatomical similarities permit..