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Gene Ontology (GO) Project http://www.geneontology.org/ Jane Lomax There is a lot of biological research output You’re interested in which genes control in mesoderm development… You get 6752 results! How will you ever find what you want? time Defense response Immune response

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slide1

Gene Ontology (GO) Project

http://www.geneontology.org/

Jane Lomax

slide2

There is a lot

of biological

research output

slide4

You get 6752

results!

How will you

ever find what

you want?

slide5

time

Defense response

Immune response

Response to stimulus

Toll regulated genes

JAK-STAT regulated genes

Puparial adhesion

Molting cycle

hemocyanin

Amino acid catabolism

Lipid metobolism

Peptidase activity

Protein catabloism

Immune response

Immune response

Toll regulated genes

control

attacked

Microarray data

shows changed

expression of

thousands of genes.

How will you spot the patterns?

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

slide6

Scientists

work hard

slide7

There are

lots of papers

to read

http://www.teamtechnology.co.uk/f-scientist.jpg

slide8

More papers…

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slide9

more and

more

and more…

http://www.teamtechnology.co.uk/f-scientist.jpg

slide10

Help!

more and

more

and more!

http://www.teamtechnology.co.uk/f-scientist.jpg

slide11

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

slide16

Definition of

mesoderm

development

Gene products

involved in

mesoderm

development

microarray process
Microarray process:
  • Treat samples
  • Collect mRNA
  • Label
  • Hybridize
  • Scan
  • Normalize
  • Select differentially regulated genes
  • Understand the biological phenomena involved
traditional analysis
Traditional analysis
  • gene by gene basis
  • requires literature searching
  • time-consuming
traditional analysis20

Gene 1

Apoptosis

Cell-cell signaling

Protein phosphorylation

Mitosis

Gene 2

Growth control

Mitosis

Oncogenesis

Protein phosphorylation

Gene 3

Growth control

Mitosis

Oncogenesis

Protein phosphorylation

Gene 4

Nervous system

Pregnancy

Oncogenesis

Mitosis

Gene 100

Positive ctrl. of cell prolif

Mitosis

Oncogenesis

Glucose transport

Traditional analysis
using go annotations

GO:0006915 : apoptosis

Using GO annotations
  • But by using GO annotations, this work has already been done
grouping by process
Grouping by process

Mitosis

Gene 2

Gene 5

Gene45

Gene 7

Gene 35

Glucose transport

Gene 7

Gene 3

Gene 6

Apoptosis

Gene 1

Gene 53

Positive ctrl. of

cell prolif.

Gene 7

Gene 3

Gene 12

Growth

Gene 5

Gene 2

Gene 6

go for microarray analysis
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?
slide24

How does the

Gene Ontology work?

go structure
GO structure
  • GO isn’t just a flat list of biological terms
  • terms are related within a hierarchy
go structure27
GO structure
  • This means genes can be grouped according to user-defined levels
  • Allows broad overview of gene set or genome
how does go work
How does GO work?

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

how does go work29
How does GO work?

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

  • What does the gene product do?
how does go work30
How does GO work?

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

  • What does the gene product do?
  • Where and when does it act?
how does go work31
How does GO work?

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

  • What does the gene product do?
  • Where and when does it act?
  • Why does it perform these activities?
go structure32
GO structure
  • GO terms divided into three parts:
    • cellular component
    • molecular function
    • biological process
cellular component
Cellular Component
  • where a gene product acts
cellular component36
Cellular Component
  • Enzyme complexes in the component ontology refer to places, not activities.
molecular function
Molecular Function
  • activities or “jobs” of a gene product

glucose-6-phosphate isomerase activity

molecular function38
Molecular Function

insulin binding

insulin receptor activity

molecular function39
Molecular Function

drug transporter activity

molecular function40
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
biological process

cell division

Biological Process

a commonly recognized series of events

biological process42
Biological Process

transcription

biological process43
Biological Process

regulation of gluconeogenesis

biological process44
Biological Process

limb development

biological process45
Biological Process

courtship behavior

ontology structure
Ontology Structure
  • Terms are linked by two relationships
    • is-a 
    • part-of 
ontology structure47

cell

membrane chloroplast

mitochondrial chloroplast

membrane membrane

is-a

part-of

Ontology Structure
ontology structure48
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
ontology structure49
Ontology Structure

cell

membrane chloroplast

mitochondrial chloroplast

membrane membrane

Directed Acyclic Graph (DAG) - multiple parentage allowed

anatomy of a go term
Anatomy of a GO term

unique GO ID

id: GO:0006094

name: gluconeogenesis

namespace: process

def: The formation of glucose from

noncarbohydrate precursors, such as

pyruvate, amino acids and glycerol.

[http://cancerweb.ncl.ac.uk/omd/index.html]

exact_synonym: glucose biosynthesis

xref_analog: MetaCyc:GLUCONEO-PWY

is_a: GO:0006006

is_a: GO:0006092

term name

ontology

definition

synonym

database ref

parentage

slide52

In biology…

Taction

Tactition

Tactile sense

?

slide53

Tactition

Taction

Tactile sense

perception of touch ; GO:0050975

slide55

= tooth bud initiation

= cellular bud initiation

= flower bud initiation

slide56

Categorization of gene products

using GO is called annotation.

So how does that happen?

slide57

P05147

Take a gene or protein

slide58

P05147

PMID: 2976880

Find papers

about it

slide59

P05147

GO:0047519

PMID: 2976880

Find the GO

term describing its

function, process

or location of action.

slide60

P05147

PMID: 2976880

IDA

What

evidence

do they

show?

GO:0047519

slide61

P05147

GO:0047519

P05147 GO:0047519 IDA PMID:2976880

PMID: 2976880

IDA

Record these:

slide64

Clark et al., 2005

Many species

groups annotate

We see the

research of one

function across

all species

slide65

Adding terms

to the GO

developing go
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
slide71

2006 Consortium Meeting,

St. Croix,

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

slide72

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)

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