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..