The Gene Ontology project

Jane Lomax

Ontology (for our purposes)

• “an explicit specification of some topic” – Stanford Knowledge Systems Lab

• Includes:– a vocabulary of terms (names)– defined logical relationships to each

• Compile structured vocabularies describing aspects of molecular biology

• Describe gene products using vocabulary terms (annotation)

• Develop tools:• to query and modify the vocabularies and annotations• annotation tools for curators

GO Project Goals:

•Molecular Function — elemental activity or task

•Biological Process — broad objective or goal

•Cellular Component — location or complex

The Three Ontologies

•Molecular Function — elemental activity or tasknuclease, DNA binding, transcription factor

•Biological Process — broad objective or goal

•Cellular Component — location or complex

The Three Ontologies

•Molecular Function — elemental activity or tasknuclease, DNA binding, transcription factor

•Biological Process — broad objective or goalmitosis, signal transduction, metabolism

•Cellular Component — location or complex

The Three Ontologies

•Molecular Function — elemental activity or tasknuclease, DNA binding, transcription factor

•Biological Process — broad objective or goalmitosis, signal transduction, metabolism

•Cellular Component — location or complexnucleus, ribosome, origin recognition complex

The Three Ontologies

DAG Structure

Directed acyclic graph: each child may have one or more parents

Every path from a node back to the root must be biologically accurate

The True Path Rule

True Path Rule

Chitin biosynthesis

Chitin catabolism

chitin metabolism

Cuticle synthesis

Cell wall biosynthesis

GO process

chitin metabolism

Cuticle biosynthesis

Cell wall biosynthesis

New GO Terms

cell wall chitin biosynth.

cell wall chitin catab.

cuticle chitin biosynth.

cuticle chitin catab

cell wall chitin metab.

chitin catabo-lism

chitin biosynthesis

cuticle chitin metab.

GO process

cell wall bio-synthesis (fungi)

chitin metabolism

cuticle synthesis

cell wall chitin catab.

chitin catabo-lism

chitin metabolism

cell wall chitin metab.

cell wall bio-synthesis

• is-asubclass; a is a type of b

• part-ofphysical part of (component)subprocess of (process)

Relationship Types

• Not a way to unify biological databases

• Not a dictated standard

• Does not define evolutionary relationships

• Additional ontologies needed to model biology and experimentation

What GO is NOT:

• Names of gene products

• Protein domains

• Protein sequence features

• Phenotypes; diseases

• Anatomical terms (except as part of terms generated by cross-products)

Terms outside the Scope of GO

Advantages of GO

• Cross-species comparisons• already used by an increasing number of databases

• More comprehensive• many terms per gene product• not a strict hierarchy: many-to-many relationships possible

• Simplify querying• Uses restricted vocabulary developed by curators and

annotators

• Use of evidence codes

• Database object: gene or gene product

• GO term ID

• Reference

•publication or computational method

• Evidence supporting annotation

Annotation Features:

DAG Structure

Annotate to any level within DAG

• GO Annotations for:

• Human proteins

• All SWISS-PROT/TrEMBL proteins

• Annotation sets for completely sequenced proteomes

GOA: GO Annotation at EBI

• Methods:

• Manual curation

• SWISS-PROT keyword <-> GO term mapping

• EC number <-> GO term mapping

• InterPro entry <-> GO term mapping

GOA: GO Annotation at EBI

• Browsers:

• DAG-Edit

• AmiGO

• “QuickGO” at EBI

• EP:GO browser

GO Tools

• Developmental processes — DAG cross- products with anatomy terms

• Physiological processes

• Relational database

•Expand relationship types

The Future of GO:

• FlyBase & Berkeley Drosophila Genome Project • WormBase• Saccharomyces Genome Database • DictyBase• Mouse Genome Informatics • Compugen, Inc• The Arabidopsis Information Resource• Swiss-Prot/TrEMBL/InterPro

• Pathogen Sequencing Unit (Sanger Institute)

• PomBase (Sanger Institute)

• Rat Genome Database

• Genome Knowledge Base (CSHL)

• The Institute for Genomic Research

www.geneontology.org

The Gene Ontology Consortium is supported by NHGRI grant HG02273 (R01). The Gene Ontology project thanks AstraZeneca for financial support. The Stanford group acknowledges a gift from Incyte Genomics.