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Gene Ontology (GO)
Project
http://www.geneontology.org/
Jane Lomax
There is a lot
of biological
research output
http://www.geneontology.org/
You’re
interested in
which genes
control
in mesoderm
development…
http://www.geneontology.org/
You get 6752
results!
How will you
ever find what
you want?
http://www.geneontology.org/
time
Microarray data
shows changed
Defense response
Immune response
of
Response toexpression
stimulus
Toll regulated genes
thousands
of genes.
JAK-STAT regulated
genes
Puparial adhesion
Molting cycle
hemocyanin
How will you spot
the patterns?
Amino acid catabolism
Lipid metobolism
Peptidase activity
Protein catabloism
Immune response
Immune response
Toll regulated genes
attacked control
Tree:
pearson
Coloredby:
by:
rson lw n3d
... lw n3d ... Colored
ssification:
Set_LW_n3d_5p_...
Gene
List:
_LW_n3d_5p_...
Gene
List:
Bregje Wertheim at the Centre for Evolutionary Genomics,
Department of Biology, UCL and Eugene Schuster Group, EBI.
Copy
of Copy
C5_RMA
Copy
ofofCopy
of(Defa...
C5_RMA (Defa...
allall
genes
(14010)(14010)
genes
http://www.geneontology.org/
Scientists
work hard
http://www.geneontology.org/
There are
lots of papers
to read
http://www.teamtechnology.co.uk/f-scientist.jpg
More papers…
http://www.teamtechnology.co.uk/f-scientist.jpg
more and
more
and more…
http://www.teamtechnology.co.uk/f-scientist.jpg
more and
more
and more!
Help!
http://www.teamtechnology.co.uk/f-scientist.jpg
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
http://www.geneontology.org/
http://www.geneontology.org/
Definition of
mesoderm
development
Gene
products
involved in
mesoderm
development
http://www.geneontology.org/
• GO can be used to help analyse
microarray data
http://www.geneontology.org/
Microarray process:
•
•
•
•
•
•
•
•
Treat samples
Collect mRNA
Label
Hybridize
Scan
Normalize
Select differentially regulated genes
Understand the biological phenomena involved
http://www.geneontology.org/
Traditional analysis
• gene by gene basis
• requires literature searching
• time-consuming
http://www.geneontology.org/
Traditional analysis
Gene 1
Apoptosis
Cell-cell signaling
Protein phosphorylation
Mitosis
…
Gene 3
Growth control
Gene 4
Mitosis
Nervous system
Oncogenesis
Pregnancy
Protein phosphorylation
Oncogenesis
…
Mitosis
…
Gene 2
Growth control
Mitosis
Oncogenesis
Protein phosphorylation
…
Gene 100
Positive ctrl. of cell prolif
Mitosis
Oncogenesis
Glucose transport
…
http://www.geneontology.org/
Using GO annotations
• But by using GO annotations, this work
has already been done
GO:0006915 : apoptosis
http://www.geneontology.org/
Grouping by process
Apoptosis
Gene 1
Gene 53
Positive ctrl. of
cell prolif.
Gene 7
Gene 3
Gene 12
…
Mitosis
Gene 2
Gene 5
Gene45
Gene 7
Gene 35
…
Glucose transport
Gene 7
Gene 3
Gene 6
…
Growth
Gene 5
Gene 2
Gene 6
…
http://www.geneontology.org/
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?
http://www.geneontology.org/
How does the
Gene Ontology work?
http://www.geneontology.org/
GO structure
• GO isn’t just a flat list of
biological terms
• terms are related within
a hierarchy
http://www.geneontology.org/
GO structure
gene
A
http://www.geneontology.org/
GO structure
• This means genes
can be grouped
according to userdefined levels
• Allows broad
overview of gene
set or genome
http://www.geneontology.org/
How does GO work?
What information might we want to
capture about a gene product?
http://www.geneontology.org/
How does GO work?
What information might we want to
capture about a gene product?
• What does the gene product do?
http://www.geneontology.org/
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?
http://www.geneontology.org/
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?
http://www.geneontology.org/
GO structure
• GO terms divided into three parts:
– cellular component
– molecular function
– biological process
http://www.geneontology.org/
Cellular Component
• where a gene product acts
http://www.geneontology.org/
Cellular Component
http://www.geneontology.org/
Cellular Component
http://www.geneontology.org/
Cellular Component
• Enzyme complexes in the component
ontology refer to places, not activities.
http://www.geneontology.org/
Molecular Function
• activities or “jobs” of a gene product
glucose-6-phosphate isomerase activity
http://www.geneontology.org/
Molecular Function
insulin binding
insulin receptor activity
http://www.geneontology.org/
Molecular Function
drug transporter activity
http://www.geneontology.org/
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
http://www.geneontology.org/
Biological Process
a commonly recognized series of events
cell division
http://www.geneontology.org/
Biological Process
transcription
http://www.geneontology.org/
Biological Process
regulation of gluconeogenesis
http://www.geneontology.org/
Biological Process
limb development
http://www.geneontology.org/
Biological Process
courtship behavior
http://www.geneontology.org/
Ontology Structure
• Terms are linked by two relationships
– is-a
– part-of


http://www.geneontology.org/
Ontology Structure
cell
membrane
mitochondrial
membrane
is-a
part-of
chloroplast
chloroplast
membrane
http://www.geneontology.org/
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
http://www.geneontology.org/
Ontology Structure
cell
membrane
mitochondrial
membrane
Directed Acyclic Graph
(DAG) - multiple
parentage allowed
chloroplast
chloroplast
membrane
http://www.geneontology.org/
Anatomy of a GO term
id: GO:0006094
unique GO ID
name: gluconeogenesis
term name
ontology
namespace: process
def: The formation of glucose from
noncarbohydrate precursors, such as
definition
pyruvate, amino acids and glycerol.
[http://cancerweb.ncl.ac.uk/omd/index.html]
exact_synonym: glucose biosynthesis
synonym
xref_analog: MetaCyc:GLUCONEO-PWY
database ref
is_a: GO:0006006
parentage
is_a: GO:0006092
http://www.geneontology.org/
GO can also be useful for resolving
language conflicts amongst scientific
communities
http://www.geneontology.org/
In biology…
Tactition
Taction
Tactile sense
?
http://www.geneontology.org/
Tactition
Taction
Tactile sense
perception of touch ; GO:0050975
http://www.geneontology.org/
Bud initiation?
http://www.geneontology.org/
= tooth bud initiation
= cellular bud initiation
= flower bud initiation
http://www.geneontology.org/
Categorization of gene products
using GO is called annotation.
So how does that happen?
http://www.geneontology.org/
P05147
Take a gene or
protein
http://www.geneontology.org/
P05147
Find papers
about it
PMID: 2976880
http://www.geneontology.org/
P05147
PMID: 2976880
Find the GO
term describing its
function, process
or location of action.
GO:0047519
http://www.geneontology.org/
P05147
PMID: 2976880
What
evidence
do they
show?
IDA
GO:0047519
http://www.geneontology.org/
P05147
PMID: 2976880
Record these:
P05147
GO:0047519
IDA
PMID:2976880
IDA
GO:0047519
http://www.geneontology.org/
Submit to the GO Consortium
http://www.geneontology.org/
Annotation appears in GO database
http://www.geneontology.org/
Clark et al., 2005
Many species
groups annotate
We see the
research of one
function across
all species
http://www.geneontology.org/
Adding terms
to the GO
http://www.geneontology.org/
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
http://www.geneontology.org/
http://www.geneontology.org/
http://www.geneontology.org/
http://www.geneontology.org/
http://www.geneontology.org/
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)
http://www.geneontology.org/