GO : the Gene Ontology

“because you know sometimeswords have two meanings”

Amelia IrelandGO Curator

EBI, Cambridge, UK

What’s in a name?

• What is a cell?

Cell

Cell

Cell

Cell

Cell

Cell

Image from http://microscopy.fsu.edu

Cell

• A cell can be a part or a whole organism

Images from http://microscopy.fsu.edu

What’s in a name?

What’s in a name?

• Glucose synthesis• Glucose biosynthesis• Glucose formation• Glucose anabolism• Gluconeogenesis

• All refer to the process of making glucose from simpler components

What’s in a name?

• Same name for different concepts• Different names for the same concept• Vast amounts of biological data from

different sources

Cross-species or cross-database comparison is difficult

The problem:

What is the Gene Ontology?

• A (part of the) solution: The Gene Ontology: “a controlled

vocabulary that can be applied to all organisms even as knowledge of gene and protein roles in cells is accumulating and changing”

• A controlled vocabulary to describe gene products - proteins and RNA - in any organism.

What is GO?

• One of the Open Biological Ontologies

• Standard, species-neutral way of representing biology

• Three structured networks of defined terms to describe gene product attributes

• More like a phrase book than a biology text book

How does GO work?

• What does the gene product do?• Where and when does it act?• Why does it perform these activities?

What information might we want to capture about a gene product?

No GO Areas

• GO covers ‘normal’ functions and processes No pathological processes No experimental conditions

• NO evolutionary relationships• NO gene products• NOT a system of nomenclature

Cellular Component

• where a gene product acts

Cellular Component

Cellular Component

Cellular Component

• Enzyme complexes in the component ontology refer to places, not activities.

Molecular Function

• activities or “jobs” of a gene product

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are needed to see this picture.

glucose-6-phosphate isomerase activity

Molecular Function

insulin bindinginsulin receptor activity

Molecular Function

drug transporter activity

Molecular Function

• A gene product may have several functions; a function term refers to a single reaction or activity, not a gene product.

• Sets of functions make up a biological process.

Biological Process

a commonly recognized series of events

cell division

Biological Process

transcription

Biological Process

regulation of gluconeogenesis

Biological Process

limb development

Biological Process

courtship behavior

Anatomy of a GO term

id: GO:0006094name: gluconeogenesisnamespace: processdef: The formation of glucose fromnoncarbohydrate precursors, such aspyruvate, amino acids and glycerol.[http://cancerweb.ncl.ac.uk/omd/index.html]exact_synonym: glucose biosynthesisxref_analog: MetaCyc:GLUCONEO-PWYis_a: GO:0006006is_a: GO:0006092

unique GO IDterm name

definition

synonymdatabase ref

parentage

ontology

Anatomy of a GO term

• Species-specific terms use the phrase “sensu xxx” - ‘in the sense of’

• stalk formation sensu Plantae: slender or elongated

structure that supports a plant, plant part or plant organ

sensu Dictyostelium: a tubular structure that consists of cellulose-covered cells stacked on top of each other and surrounded by an acellular stalk tube composed of cellulose and glycoprotein.

Anatomy of a GO term

• GO synonyms include alternative wordings, spellings, and related concepts Broader, narrower, exact or related Useful search aid

name: glucose transportexact_synonym: gluco-hexose transportnarrow_synonym: glucose shuttling

Ontology Structure

• Ontologies are structured as a hierarchical directed acyclic graph

• Terms can have more than one parent and zero, one or more children

• Terms are linked by two relationships is-a part-of

Ontology Structure

cell

membrane chloroplast

mitochondrial chloroplastmembrane membrane

is-apart-of

True Path Rule

• The path from a child term all the way up to its top-level parent(s) must always be true

cell nucleus

chromosome

But what about bacteria?

True Path Rule

Resolved component ontology structure:

cell cytoplasm

chromosome nuclear chromosome

nucleus nuclear chromosome

GO for it!

• GO to

http://www.ebi.ac.uk/~aji/intro.html

GO Annotation

• Using GO terms to represent the activities and localizations of a gene product

• Annotations contributed by members of the GO Consortium model organism databases cross-species databases, eg. UniProt

• Annotations freely available from GO website

GO Annotation

• Database object gene or gene product

• GO term ID e.g. GO:0003677

• Reference for annotation e.g. PubMed paper, BLAST results

• Evidence code from evidence code ontology

GO Annotation

• Electronic annotation from mappings files

e.g. UniProt keyword2go

High quantity but low quality Annotations to low level terms Not checked by curators

• Manual annotation From literature curation Time consuming but high quality

GO Annotation

ISS Inferred from Sequence/Structural SimilarityIDA Inferred from Direct AssayIPI Inferred from Physical InteractionTAS Traceable Author StatementNAS Non-traceable Author StatementIMP Inferred from Mutant PhenotypeIGI Inferred from Genetic InteractionIEP Inferred from Expression PatternIC Inferred by CuratorND No Data available

IEA Inferred from electronic annotation

GO Annotate

In this study, we report the isolation and molecular characterization of the B. napus PERK1 cDNA, that is predicted to encode a novel receptor-like kinase. We have shown that like other plant RLKs, the kinase domain of PERK1 has serine/threonine kinase activity. In addition, the location of a PERK1-GTP fusion protein to the plasma membrane supports the prediction that PERK1 is an integral membrane protein…these kinases have been implicated in early stages of wound response…

Function: protein serine/threonine kinase activity ; GO:0004674 (IDA)

Component:integral to plasma membrane ; GO:0005887 (IDA)

Process: response to wounding ; GO:0009611 (NAS)

GO for it (again)!

• GO to

http://www.ebi.ac.uk/~aji/annotI.html