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Integrating phenotype ontologies across multiple species
Caltech 2009
Chris Mungall
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Conservation of phenotypes
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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?
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Anatomical and structural entities in OBO
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MP MP-is_a hierarchy-hand-crafted
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PATO EQ Descriptions
• PATO:– ontology of qualities
• EQ Descriptions– An expression consisting of:• a PATO ID (Q)• A bearer entity (E)• Optional additional tags
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Examples
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Relational Qualities
Have a bearer - have an additional dependency on some type of entity
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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
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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>
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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
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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
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Methodologies
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Unifying descriptions
Equivalence MappingsbetweentermEQ expression
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Methods
• Use obol to generate first pass and updates– parses term name– assumes semi-controlled syntax
• Manually edit obo xp file
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Results
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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
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Reasoning
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Reasoner Results: HP/MP
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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)
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Mapping AOs to Uberon
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Phenoblast: Quantifying similarity
SimJ: 0.42MaxIC: 13.4
SimJ: 0.32MaxIC: 12.1
SimJ: 0.17MaxIC: 6.2
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Recoveringpathwaymembersby phenotypicsimilarity
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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..