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An International Centre for Mouse Genetics
EuroPhenome and the International
Mouse Phenotyping Consortium
John Hancock
MRC Harwell
“High throughput” phenotyping
• Systematic phenotyping of a mouse line using
a battery of simple tests to detect defects in
as many body systems as possible
• e.g. SHIRPA
• Obtains the maximum coverage of
phenotype in the shortest possible time
• Still takes c. 15 weeks
An International Centre for Mouse Genetics
High Throughput Phenotyping
• EUMODIC
• Generate knockout ES cells (EUCOMM,
KOMP, NorCOMM)
• Make mice
• Carry out high throughput phenotyping
using standardised protocols (SOPs)
• Provide data to wider community via a
database
An International Centre for Mouse Genetics
EMPReSS-slim - Pipeline for High
Throughput Phenotyping
An International Centre for Mouse Genetics
EMPReSS
• 86 Standard operating procedures (SOPs)
• (Dys)morphology
• Cardiovascular
• Metabolic
• Haematology/Clinical Chemistry
• Allergy/Immunology
• Behaviour
• Sensory
• Pathology
http://empress.har.mrc.ac.uk
An International Centre for Mouse Genetics
An International Centre for Mouse Genetics
EuroPhenome - Data Capture
• MIMPP-compliant data
files (XML)
• Nightly XML file upload
from phenotyping centres
• Validation with EMPReSS
e.g.
Parameters/units/bounds
An International Centre for Mouse Genetics
Validation
EuroPhenome http:www.europhenome.eu
An International Centre for Mouse Genetics
The EQ + PATO Approach
• E = Entity, e.g. tail, derived from an ontology
such as anatomy
• Q = Quality, derived from the Quality
Ontology PATO
• Can be used to build up a description of an
atom of phenotypic data…
An International Centre for Mouse Genetics
E+Q - An Example
Currently in use in EuroPhenome DB
An International Centre for Mouse Genetics
“Mine for a Mutant” in EuroPhenome
An International Centre for Mouse Genetics
Finding Phenodeviants via MouseBook
An International Centre for Mouse Genetics
View from EuroPhenome
An International Centre for Mouse Genetics
International Mouse Phenotyping Consortium
1st Aim: To characterise the phenotype of c. 20,000
mouse gene knockouts in the next 10 years
• Establish new phenotyping centres (Infrafrontier)
• Develop the EMPReSSslim pipeline to provide the
best possible first-line screen
• Informatics Discussion…
An International Centre for Mouse Genetics
IMPC Informatics
EUMODIC as a model
What lessons can be learnt?
Tear it up and start again?
Access to data
As quick as possible
QC?
Single IMPC portal (but DB should provide WS
access)
Big Question:
One single database? (location?)
Continental level repositories (identical
infrastructure?)
Many individual, interlinked DBs
An International Centre for Mouse Genetics
Phenobabelomics
Need Efforts To Facilitate The Linking Of
These Data Sets
Detailed
Descriptions
Mutant Data
Baseline Data
An International Centre for Mouse Genetics
Protocols
Interphenome (MPDIC) Consortium
Mammalian Genome 18, 157-163 (2007)
An International Centre for Mouse Genetics
Three broad requirements
• Common data description
• Common protocol description
• Standard for data exchange
Interphenome discussion are ongoing
Last meeting in Prague (2 Nov 08)
An International Centre for Mouse Genetics
Mouse Models, Human Disease
How to we relate mouse phenotypes to human
diseases?
• Diseases are made up of individual
phenotypes, as we understand them
• Presence of only a subset of phenotypes may
be enough to diagnose a disease
• Phenotype -> OMIM mapping not good
enough
An International Centre for Mouse Genetics
Mouse Phenotype to Human Disease
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DISEASE
Interpreter
Phenotypic Attributes
Phenotypic Attributes
Phenotypic Attributes
Phenotypic Attributes
Phenotypic Attributes
Phenotypic Attributes
Phenotypic Measures
An International Centre for Mouse Genetics
Phenotypic Measures
Phenotypic Attributes
Phenotypic Measures
PHENOTYPING
Thanks To…
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Ann-Marie Mallon
Andy Blake
Simon Greenaway
Tim Beck
Hugh Morgan
Octavio Espinosa
Georgios Gkoutos
Eain Green
Joe Weekes
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Paul Schofield
Christoph Lengger
Hiroshi Masuya
EUMORPHIA
EUMODIC
The Interphenome group
CASIMIR
MRC and the EU for funding
An International Centre for Mouse Genetics
An International Centre for Mouse Genetics
Use of Ontologies in EuroPhenome:
What is an Ontology?
Essentially a controlled vocabulary with defined
relationships and definitions, e.g.:
Head
Sensory Organ
{Is_A}
{Part_Of}
Ear
Nose
Brain
Ear
Nose
Tongue
Allows us, for example, to identify other parts of the head
that might be affected
An International Centre for Mouse Genetics
E+Q - An Example
E: tail + Q: length [assayed by] measurement of tail length by ruler [unit] cm
returns
value
Q: increased length
5
Inferred qualitative description
Long tail
MP:0002758
Normal value, e.g.
from EuroPhenome
Currently in use in EuroPhenome DB
An International Centre for Mouse Genetics
High Throughput Phenotyping EUMORPHIA and EUMODIC
EUMORPHIA
• FP5 project involving 19 partners
• Generate standard set of phenotyping SOPs
• EMPReSS: European Mouse Phenotyping
Resource for Standardised Screens
• EMPReSS online resource
An International Centre for Mouse Genetics
IMPC Informatics
• Compatibility between centres - schemas for exporting
data into compatible format - share software
• Single site for user to view data - raw data, analysis
tools
• Dedicated group (neutral?)
• Unified, central database?
• Build on current efforts/rebuild?
• Networked closely to phenotyping centres - responsible
for information standards, ontology development etc.
• Dissemination
• Genome browser
• Search on phenotype ontology terms e.g. at MGI
• Links with OMIM, search from human phenotypes
(mapping mouse phenotypes onto human and vice versa)
An International Centre for Mouse Genetics
IMPC Informatics
• Analysis
• Many tools already available
• Compare allele to allele to wild type
• Internal organisation - coordination
• Cross-talk - committees/groups (including external
experts) to leverage and learn from ongoing efforts in
data outputs/capture/data structure…
• InterPhenome as an example - extend, introduce
experts and advisory board
• Wikis for genes
• Need dollars/euros
• Data release
• As the data is generated - need formal agreement
• Resources: 20-40 people? Need considerable
investment
An International Centre for Mouse Genetics