Gene Ontology (GO) Project

http://www.geneontology.org/

Jane Lomax

http://www.geneontology.org/

There is a lotof biological research output

http://www.geneontology.org/

You’re interested in which genes control inmesoderm development…

http://www.geneontology.org/

You get 6752results!

How will you ever find whatyou want?

http://www.geneontology.org/Selected Gene Tree: pearson lw n3d ...Branch color classification:Set_LW_n3d_5p_...

Colored by: Copy of Copy of C5_RMA (Defa...Gene List: all genes (14010)

attacked

time

control

Puparial adhesionMolting cyclehemocyanin

Defense responseImmune responseResponse to stimulusToll regulated genesJAK-STAT regulated genes

Immune responseToll regulated genes

Amino acid catabolismLipid metobolism

Peptidase activityProtein catabloismImmune response

Selected Gene Tree: pearson lw n3d ...Branch color classification:Set_LW_n3d_5p_...

Colored by: Copy of Copy of C5_RMA (Defa...Gene List: all genes (14010)

Bregje Wertheim at the Centre for Evolutionary Genomics, Department of Biology, UCL and Eugene Schuster Group, EBI.

Microarray datashows changed expression ofthousands of genes.

How will you spot the patterns?

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Scientistswork hard

There arelots of papersto read

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More papers…

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more andmoreand more…

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Help!more andmoreand more!

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The Gene Ontology provides a way to capture and represent biological all this knowledge in a computable form

http://www.geneontology.org/

The Gene Ontology

http://www.geneontology.org/

GO browser

http://www.geneontology.org/

Search on ‘mesoderm development’

mesoderm development

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http://www.geneontology.org/

Definition of mesodermdevelopment

Gene productsinvolved in mesodermdevelopment

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• GO can be used to help analyse microarray data

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Microarray process:

• Treat samples• Collect mRNA• Label• Hybridize• Scan• Normalize• Select differentially regulated genes • Understand the biological phenomena involved

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Traditional analysis

• gene by gene basis

• requires literature searching

• time-consuming

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Traditional analysisGene 1ApoptosisCell-cell signalingProtein phosphorylationMitosis…

Gene 2Growth controlMitosisOncogenesisProtein phosphorylation…

Gene 3Growth controlMitosisOncogenesisProtein phosphorylation…

Gene 4Nervous systemPregnancyOncogenesisMitosis…

Gene 100Positive ctrl. of cell prolifMitosisOncogenesisGlucose transport…

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Using GO annotations

• But by using GO annotations, this work has already been done

GO:0006915 : apoptosis

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Grouping by process

ApoptosisGene 1Gene 53

MitosisGene 2Gene 5Gene45Gene 7Gene 35…

Positive ctrl. of cell prolif.Gene 7Gene 3Gene 12…

GrowthGene 5Gene 2Gene 6…

Glucose transportGene 7Gene 3Gene 6…

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GO for microarray analysis

• Annotations give ‘function’ label to genes

• Ask meaningful questions of microarray data e.g.– genes involved in the same process,

same/different expression patterns?

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How does theGene Ontology work?

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GO structure• GO isn’t just a flat list

of biological terms• terms are related

within a hierarchy

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GO structure

gene A

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GO structure

• This means genes can be grouped according to user-defined levels

• Allows broad overview of gene set or genome

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How does GO work?

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

http://www.geneontology.org/

How does GO work?

• What does the gene product do?

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

http://www.geneontology.org/

How does GO work?

• What does the gene product do?• Where and when does it act?

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

http://www.geneontology.org/

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

http://www.geneontology.org/

GO structure

• GO terms divided into three parts:– cellular component– molecular function– biological process

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Cellular Component

• where a gene product acts

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Cellular Component

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Cellular Component

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Cellular Component

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

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Molecular Function

• activities or “jobs” of a gene product

glucose-6-phosphate isomerase activity

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Molecular Function

insulin bindinginsulin receptor activity

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Molecular Function

drug transporter activity

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Molecular Function

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

• Sets of functions make up a biological process

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Biological Process

a commonly recognized series of events

cell division

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Biological Process

transcription

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Biological Process

regulation of gluconeogenesis

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Biological Process

limb development

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Biological Process

courtship behavior

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Ontology Structure

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

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Ontology Structurecell

membrane chloroplast

mitochondrial chloroplastmembrane membrane

is-apart-of

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Ontology Structure

• Ontologies are structured as a hierarchical directed acyclic graph (DAG)

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

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Ontology Structure

cell

membrane chloroplast

mitochondrial chloroplastmembrane membrane

Directed Acyclic Graph (DAG) - multiple

parentage allowed

http://www.geneontology.org/

Anatomy of a GO termid: 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

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GO can also be useful for resolving language conflicts amongst scientific communities

http://www.geneontology.org/

TactitionTactile sense

Taction

?

In biology…

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TactitionTactile sense

Taction

perception of touch ; GO:0050975

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Bud initiation?

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= tooth bud initiation

= cellular bud initiation

= flower bud initiation

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Categorization of gene productsusing GO is called annotation.

So how does that happen?

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P05147

Take a gene or protein

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P05147

PMID: 2976880

Find papersabout it

http://www.geneontology.org/

P05147 PMID: 2976880

GO:0047519

Find the GO term describing itsfunction, process or location of action.

http://www.geneontology.org/

P05147

PMID: 2976880

IDA

GO:0047519

What evidencedo theyshow?

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P05147

PMID: 2976880

GO:0047519

IDA

P05147 GO:0047519 IDA PMID:2976880

Record these:

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Submit to the GO Consortium

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Annotation appears in GO database

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Clark et al., 2005

Many species groups annotate

We see the research of one function across all species

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Adding terms to the GO

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Developing GO

• GO under constant development• International group of developers

– central editorial office at EBI - 4 members

• Developed in consultation with domain experts– Term suggestions handled through online

tracking system

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http://www.geneontology.org/

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2006 Consortium Meeting,

St. Croix,

U.S. Virgin Islands, March 30 - April 3, 2006

http://www.geneontology.org/

Contributors

dictyBase FlyBase GeneDB Gramene

Reactome WormBase The GO Editorial Office

Berkeley Bioinformatics and Ontology Project (BBOP)

Gene Ontology Annotation @ EBI (GOA)

Mouse Genome Database (MGD) and Gene Expression Database (GXD)

Rat Genome Database (RGD)

Saccharomyces Genome Database (SGD)

The Arabidopsis Information Resource (TAIR)

The Institute for Genomic Research (TIGR)

Zebrafish Information Network (ZFIN)