The Gene Ontology Project

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The Gene Ontology Project
An Introduction
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There is a lot of biological research output.
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Search on mesoderm development
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You get 6752 results! How will you ever find
what you want?
Another example
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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.
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more every week.
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and more
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more and more and more!
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more and more and more!
Help!
Help!
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Ontology is a way to capture knowledge in a
written and computable form.
Computable
Computable means that the computer finds patterns
so we dont have to.
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Ebay search (keyword lead) v. Pubmed search
(keyword flower) Demo and practical work
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The Gene Ontology
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This is our browser.
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Search on mesoderm development.
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Here is mesoderm development.
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Definition of mesoderm development. Gene
products involved in mesoderm development.
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There are many gene products involved in mesoderm
development.
But fewer gene products than papers.
You can read papers describing what is
known about them.
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time
control
attacked
Bregje Wertheim at the Centre for Evolutionary
Genomics, Department of Biology, UCL and Eugene
Schuster Group, EBI.
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See which processes are upregulated or
downregulated.
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
attacked
control
Bregje Wertheim at the Centre for Evolutionary
Genomics, Department of Biology, UCL and Eugene
Schuster Group, EBI.
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Practical work Search AmiGO Did you find your
favourite gene product or process?
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How does the Gene Ontology work?
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The Gene Ontology is like a dictionary
term transcription initiation
id GO0006352
definition Processes involved in the assembly
of the RNA polymerase complex at the promoter
region of a DNA template resulting in the
subsequent synthesis of RNA from that promoter.
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The whole system.
Clark et al., 2005
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An example
Mitochondrial P450 (CC24 PR01238 MITP450CC24)
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Where is it?
Mitochondrial p450
mitochondrial inner membrane
GO cellular component term GO0005743
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What does it do?
substrate O2 CO2 H20 product
monooxygenase activity
GO molecular function term GO0004497
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Which process is this?
electron transport
GO biological process term GO0006118
http//ntri.tamuk.edu/cell/ mitochondrion/krebpic
.html
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The whole system.
Clark et al., 2005
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The Gene Ontology is for all species and that
means we have to bridge some language
barriers.
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Same name, same thing?
http//www.darknessandlight.co.uk/cambridge_photog
raphs.html
Bridge of Sighs, Cambridge.
http//www.lockeheemstra.com/italy/bridge-of-sighs
-venice.html
Ponte dei Sospiri, Venice.
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In biology
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Taction
Tactition
Tactile sense
perception of touch GO0050975
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Bud initiation?
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tooth bud initiation
reproductive bud initiation
branch bud initiation
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Demo Writing an ontology The car ontology
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• Demo The gene ontology

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Categorization of gene products using GO is
called annotation. So how does that happen?
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Choose your favourite gene.
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Find a paper about it.
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Find the GO term describing its function,
process or location of action.
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What evidence do they show?
GO0047519
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Write these down
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.
Send to the GO Consortium
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Finding annotations in a paper
for B. napus PERK1 protein (Q9ARH1)
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 proteinthese
kinases have been implicated in early stages of
wound response
serine/threonine kinase activity,
integral membrane protein
wound response
PubMed ID 12374299
Function protein serine/threonine
kinase activity GO0004674
Component integral to plasma membrane
GO0005887
Process response to wounding
GO0009611

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Annotation details
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Where to get annotations?

• Non-redundant species database
• Contains all GO annotations for given species
  other information.
• http//www.arabidopsis.org/
• Multispecies database - GOA
• Contains all GO annotations.
• http//beta.uniprot.org/

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Evidence codes
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IDA - inferred from direct assay Enzyme
assays In vitro reconstitution (e.g.
transcription) Immunofluorescence (for cellular
component) Cell fractionation (for cellular
component) Physical interaction/binding IEP -
inferred from expression pattern Transcript
levels (e.g. Northerns, microarray data) Protein
levels (e.g. Western blots) IGC - inferred from
genomic context Operon structure Syntenic
regions Pathway analysis Genome-scale analysis of
processes
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IGI - inferred from genetic interaction "Traditio
nal" genetic interactions such as suppressors,
synthetic lethals, etc. Functional
complementation Rescue experiments Inference
about one gene drawn from the phenotype of a
mutation in a different gene. IMP - inferred
from mutant phenotype Any gene
mutation/knockout Overexpression/ectopic
expression of wild-type or mutant
genes Anti-sense experiments RNAi
experiments Specific protein inhibitors Polymorphi
sm or allelic variation IPI - inferred from
physical interaction 2-hybrid interactions Co-pur
ification Co-immunoprecipitation Ion/protein
binding experiments
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ISS - inferred from sequence or structural
similarity Sequence similarity (homologue
of/most closely related to) Recognized
domains Structural similarity Southern
blotting RCA - inferred from reviewed
computational analysis Large-scale
protein-protein interaction experiments Microarray
experiments Integration of large-scale datasets
of several types Text-based computation IEA -
Inferred from Electronic Annotation NAS -
non-traceable author statement ND - no
biological data available TAS - traceable author
statement NR - not recorded
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PMID 15960829
Should we trust electronic annotations?
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http//www.geneontology.org/GO.indices.shtml
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ec2go mapping

• !version Revision 1.67
• !date Date 2008/01/21 112901
• !Mapping of GO function_ontology "enzymes" to
  Enzyme Commission Numbers.
• !original mapping by Michael Ashburner,
  Cambridge.
• !This version parsed from function.ontology on
  2008/01/15 140116
• !by Daniel Barrell, EBI, Hinxton
• !
• EC1 gt GOoxidoreductase activity GO0016491
• EC1.1 gt GOoxidoreductase activity, acting on
  CH-OH group of donors GO0016614
• EC1.1.1 gt GOoxidoreductase activity, acting on
  the CH-OH group of donors, NAD or NADP as
  acceptor GO0016616
• EC1.1.1.1 gt GOalcohol dehydrogenase activity
  GO0004022
• EC1.1.1.10 gt GOL-xylulose reductase activity
  GO0050038
• EC1.1.1.100 gt GO3-oxoacyl-acyl-carrier-protein
  reductase activity GO0004316
• EC1.1.1.101 gt GOacylglycerone-phosphate
  reductase activity GO0000140
• EC1.1.1.102 gt GO3-dehydrosphinganine reductase
  activity GO0047560
• EC1.1.1.103 gt GOL-threonine 3-dehydrogenase
  activity GO0008743
• EC1.1.1.104 gt GO4-oxoproline reductase activity
  GO0016617

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interpro2go mapping
InterPro is a database of protein families,
domains and functional sites in which
identifiable features found in known proteins
can be applied to unknown protein sequences.

• !date 2008/01/15 130124
• !Mapping of InterPro entries to GO
• !Nicola Mulder, Hinxton
• !
• InterProIPR000003 Retinoid X receptor gt GODNA
  binding GO0003677
• InterProIPR000003 Retinoid X receptor gt
  GOsteroid binding GO0005496
• InterProIPR000003 Retinoid X receptor gt
  GOregulation of transcription, DNA-dependent
  GO0006355
• InterProIPR000003 Retinoid X receptor gt
  GOnucleus GO0005634
• InterProIPR000005 Helix-turn-helix, AraC type gt
  GOtranscription factor activity GO0003700
• InterProIPR000005 Helix-turn-helix, AraC type gt
  GOintracellular GO0005622
• InterProIPR000006 Metallothionein, vertebrate gt
  GOmetal ion binding GO0046872
• InterProIPR000013 Peptidase M7, snapalysin gt
  GOextracellular region GO0005576
• InterProIPR000014 PAS gt GOsignal transducer
  activity GO0004871
• InterProIPR000015 Fimbrial biogenesis outer
  membrane usher protein gt GOtransporter activity
  GO0005215
• InterProIPR000018 P2Y4 purinoceptor gt
  GOpurinergic nucleotide receptor activity,
  G-protein coupled GO0045028
• InterProIPR000020 Anaphylatoxin/fibulin gt
  GOextracellular region GO0005576
• InterProIPR000021 Hok/gef cell toxic protein gt
  GOmembrane GO0016020
• InterProIPR000022 Carboxyl transferase gt
  GOligase activity GO0016874
• InterProIPR000023 Phosphofructokinase gt
  GO6-phosphofructokinase activity GO0003872

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Manual annotation appears in AmiGO.
Manual and electronic annotation appears in
QuickGO.
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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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Exercise Search for your favourite gene and see
if the annotation is electronic or
manual. http//www.ebi.ac.uk/ego/
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Submit new GO terms http//www.geneontology.org/
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GO slims
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Clark et al., 2005
is_a
part_of
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Clark et al., 2005
is_a
part_of
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Whole genome analysis (J. D. Munkvold et al.,
2004)
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analysis of high-throughput data according to GO
time
Puparial adhesion Molting cycle hemocyanin
Amino acid catabolism Lipid metobolism
Peptidase activity Protein catabloism Immune
response
Immune response Toll regulated genes
attacked
control
Bregje Wertheim at the Centre for Evolutionary
Genomics, Department of Biology, UCL and Eugene
Schuster Group, EBI.
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Making SlimsOBO-Edit
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Reapplying slimmed ontology to annotationsAmiGO
http//amigo.geneontology.org/
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Converting IDsPICRhttp//www.ebi.ac.uk/Tools/p
icr/
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GOOSEhttp//www.berkeleybop.org/goose
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2006 Consortium Meeting, St. Croix, U.S.
Virgin Islands, March 30 - April 3, 2006
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E. Coli hub
http//www.geneontology.org
Reactome