Many GO terms are implicitly composite

• cysteine biosynthesis • myoblast fusion• ATP synthesis coupled proton transport (ChEBI)• snoRNA catabolism• wing disc pattern formation• epidermal cell differentiation• regulation of flower development• interleukin-18 receptor complex• B-cell differentiation• dorsal ectoderm

Opaque references to other OBO ontologies

• cysteine biosynthesis (ChEBI)• myoblast fusion (Cell Type Ontology)• ATP synthesis coupled proton transport (ChEBI)• snoRNA catabolism (Sequence Ontology)• wing disc pattern formation (Drosophila anatomy)• epidermal cell differentiation (Cell Type Ontology)• regulation of flower development (Plant anatomy)• interleukin-18 receptor complex (not yet in OBO)• B-cell differentiation (Cell Type Ontology)• dorsal ectoderm (Spatial Qualifiers)

Methodology

• Make opaque references explicit• Use OBO ontologies

– ChEBI– Cell– PATO (qualities)– Anatomy/CARO

• Simplified example

GO: now

is_a

GABA biosynthesis

GABA metabolis

m

amino acid

biosynthesis

amino acid

metabolism

GO

GO+ChEBI: now

is_a

GABA biosynthesis

GABA metabolis

m

amino acid

biosynthesis

amino acid

metabolism

GO

amino acid

GABA

ChEBI

Linking GO to ChEBI

is_a

GABA biosynthesis

GABA metabolis

m

amino acid

biosynthesis

amino acid

metabolism

GO

amino acid

GABA

ChEBI

Can we find missing links?

is_a

GABA biosynthesis

GABA metabolis

m

amino acid

biosynthesis

amino acid

metabolism

GO

amino acid

GABA

ChEBI

Checking consistency

• GABA {metabolism,biosynthesis} are is_a children of amino acid derivative {metabolism,biosynthesis} in GO

• GABA is an is_a child of amino acid in ChEBI

Simple DAGs are not enough

• We want to define GO terms using ChEBI terms

• DAGs give necessary conditions• We want to give necessary and

sufficient conditions• Solution:

– Genus-differentia definitions– Aka cross-products aka intersections

Example genus-differentia definition

• A GABA metabolic process is:– A metabolic process

• That has_participant GABA

• This is saying more than simply adding a DAG link between GABA metabolic process and GABA– It allows us to do powerful reasoning

• Keeps ontologies in sync

[Term]id: GO:0009447name: putrescine catabolic processintersection_of: GO:0009056 ! catabolismintersection_of: results_in_division_of CHEBI:17148 ! putrescine

[Term]id: GO:0009448name: gamma-aminobutyric acid metabolic processintersection_of: GO:0008152 ! metabolismintersection_of: has_participant CHEBI:16865 ! gamma-aminobutyric acid

[Term]id: GO:0009449name: gamma-aminobutyric acid biosynthetic processintersection_of: GO:0009058 ! biosynthesisintersection_of: results_in_change_to CHEBI:16865 ! gamma-aminobutyric acid

[Term]id: GO:0009450name: gamma-aminobutyric acid catabolic processintersection_of: GO:0009056 ! catabolismintersection_of: results_in_division_of CHEBI:16865 ! gamma-aminobutyric acid

Results

• Mike Bada has created 2500 genus-differentia cross products between GO and ChEBI

– http://www.berkeleybop.org/ontologies/#go_xp_chebi

– Also relies on extension to OBO Relation ontology

• We can load into oboedit and see results with the oboedit reasoner…..

[Term]id: anon_chemical_16namespace: chebi_ontologyis_anonymous: trueunion_of: CHEBI:27775 ! P(1),P(3)-bis(5'-adenosyl) triphosphateunion_of: CHEBI:27529 ! P(1),P(2)-bis(5'-adenosyl) triphosphate

[Term]id: anon_chemical_17namespace: chebi_ontologyis_anonymous: trueunion_of: CHEBI:16019 ! prenolunion_of: CHEBI:26244 ! prenols

[Term]id: anon_chemical_18namespace: chebi_ontologyis_anonymous: trueunion_of: CHEBI:28266 ! fluoreneunion_of: CHEBI:24059 ! fluorenes

[Term]id: anon_chemical_19namespace: chebi_ontologyis_anonymous: trueunion_of: CHEBI:17563 ! phthalate(2-)union_of: CHEBI:30800 ! phthalate(1-)

[Term]id: GO:0015962name: diadenosine triphosphate metabolic processintersection_of: GO:0008152 ! metabolismintersection_of: has_participant anon_chemical_16