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 task nuclease, DNA binding, transcription factor Biological Process — broad objective or goal Cellular Component — location or complex The Three Ontologies

Molecular Function — elemental activity or task nuclease, DNA binding, transcription factor Biological Process — broad objective or goal mitosis, signal transduction, metabolism Cellular Component — location or complex The Three Ontologies

Molecular Function — elemental activity or task nuclease, DNA binding, transcription factor Biological Process — broad objective or goal mitosis, signal transduction, metabolism Cellular Component — location or complex nucleus, 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-a subclass; a is a type of b part-of physical 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 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.