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Gene Ontology (GO) Project geneontology/ Jane Lomax PowerPoint PPT Presentation

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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Gene Ontology (GO) Project geneontology/ Jane Lomax

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Gene Ontology (GO) Project

http://www.geneontology.org/

Jane Lomax


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There is a lot

of biological

research output


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You’re interested in which genes control inmesoderm development…


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You get 6752

results!

How will you

ever find what

you want?


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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.


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Scientists

work hard


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There are

lots of papers

to read

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


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More papers…

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


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more and

more

and more…

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


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Help!

more and

more

and more!

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


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


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The Gene Ontology


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GO browser


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Search on ‘mesoderm development’

mesoderm development


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Definition of

mesoderm

development

Gene products

involved in

mesoderm

development


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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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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


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GO:0006915 : apoptosis

Using GO annotations

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


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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


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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 the

Gene 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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gene A

GO structure


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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?


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How does GO work?

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

  • What does the gene product do?


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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?


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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?


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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 binding

insulin 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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cell division

Biological Process

a commonly recognized series of events


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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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cell

membrane chloroplast

mitochondrial chloroplast

membrane membrane

is-a

part-of

Ontology Structure


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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 chloroplast

membrane membrane

Directed Acyclic Graph (DAG) - multiple parentage allowed


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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


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


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In biology…

Taction

Tactition

Tactile sense

?


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Tactition

Taction

Tactile sense

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 products

using 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 papers

about it


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P05147

GO:0047519

PMID: 2976880

Find the GO

term describing its

function, process

or location of action.


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P05147

PMID: 2976880

IDA

What

evidence

do they

show?

GO:0047519


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P05147

GO:0047519

P05147GO:0047519 IDA PMID:2976880

PMID: 2976880

IDA

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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2006 Consortium Meeting,

St. Croix,

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


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Contributors

dictyBase FlyBaseGeneDB Gramene

ReactomeWormBase 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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