![Page 1: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/1.jpg)
An International Centre for Mouse Genetics
MINING PHENOTYPE DATABASES TO IDENTIFY MOUSE MODELS OF CLINICAL RELEVANCEMichelle Simon and Ann-Marie Mallon
![Page 2: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/2.jpg)
An International Centre for Mouse Genetics
Introduction
• Introduction – EUMODIC
• EuroPhenome (www.europhenome.org)• EMPRESS (European Mouse Phenotyping Resource of Standardised Screens) )• Data capture procedure.• Data display / Website.• Other phenotyping portals – Sanger mouse portal, K312 Portal
• IMPC • Overview of IMPC• MPI2 Consortium • Informatics Plans
• Worked Example.
• Tasks.
![Page 3: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/3.jpg)
An International Centre for Mouse Genetics
INTRODUCTION - EUMODIC
• EUMODIC • Pilot project to phenotype 500 mouse mutants using standardised
pipelines called EMPReSSlim (battery of simple tests to detect defects in as many body systems as possible)
• e.g. SHIRPA, Clinical Chemistry etc• Actual phenotype measurements are captured
![Page 4: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/4.jpg)
An International Centre for Mouse Genetics
INTRODUCTION – EUMODIC (II)
• Partners• MRC Harwell UK • Institut Clinique de la Souris France • Helmholtz Zentrum München Germany • The Wellcome Trust Sanger Institute UK • CMHD, Canada
• Each clinic has its own version of the phenotyping pipelines
• EuroPhenome (www.europhenome.org)• Raw and automatically annotated phenotype data from high
throughput projects such as EUMODIC
![Page 5: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/5.jpg)
An International Centre for Mouse Genetics
EuroPhenome Data Capture
SOPs Definition
Defining data Standards
Data Capture in LIMS
Data Export to Centralised DB
Validation and QC
![Page 6: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/6.jpg)
An International Centre for Mouse Genetics
EMPRESS (EUROPEAN MOUSE PHENOTYPING RESOURCE OF STANDARDISED SCREENS)
![Page 7: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/7.jpg)
An International Centre for Mouse Genetics
EMPRESS
• Experimental Procedures designed by Scientists
• Standard operating procedures (SOPs).
• SOPs stored in EMPReSS RDBMS
• Standardised Mouse Phenotyping (across centres and consortiums)• Defined measured parameters with bounds• Defined derived parameters• Environmental and other Metadata recorded• Ontology Annotation (Mammalian Phenotype and Entity Quality
PATO approaches)
![Page 8: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/8.jpg)
An International Centre for Mouse Genetics
EMPRESS
http://empress.har.mrc.ac.uk/• Comprehensive database of standardised phenotyping protocols.
Search procedures
![Page 9: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/9.jpg)
An International Centre for Mouse Genetics
EMPRESS
Four different phenotyping pipelines
Procedures
![Page 10: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/10.jpg)
An International Centre for Mouse Genetics
EMPReSS
Unique Empress Identifier
Different Parameters
Measurement types and
increments
Ontology Annotation - Mammalian Phenotype
![Page 11: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/11.jpg)
An International Centre for Mouse Genetics
EMPReSS SLIM, Primary Phenotyping Screen
21 different procedures
![Page 12: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/12.jpg)
An International Centre for Mouse Genetics
Phenotype Data Capture
Automatic data annotation of significant phenodeviants with MP ontology terms
![Page 13: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/13.jpg)
An International Centre for Mouse Genetics
EuroPhenome Data Annotation Model
Mutant Cohort
Data for 1 parameter or derived parameter
Compared to the control cohort or running baseline control
Statistical Analysis (Mann U
Whitney/T-test or
Fishers Exact)
Mean, SD, SE and P
value calculated
If P value is significant
annotate with MP term from
EMPReSS which is assigned to
that parameter
Stored in Annotati
on Database
![Page 14: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/14.jpg)
An International Centre for Mouse Genetics
EUROPHENOME STATISTICSN
umbe
r of L
ines
Sep-08
Nov-08
Jan-09
Mar-09
May-09
Jul-09
Sep-09
Nov-09
Jan-10
Mar-10
May-10
Jul-10
Sep-10
Nov-10
Jan-11
Mar-11
May-11
Jul-11
Sep-11
Nov-11
Jan-12
Mar-12
May-12
0
100
200
300
400
500
600
![Page 15: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/15.jpg)
An International Centre for Mouse Genetics
Data in Europhenome
• 502Lines
•2,505
• 30,276 Mice
HMGU MRC_Harwell WTSI ICS CMHD0
20
40
60
80
100
120
140
Centre
Num
ber o
f Alle
les w
ith P
heno
type
dat
a in
EP
![Page 16: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/16.jpg)
An International Centre for Mouse Genetics
Number of Lines with significant annotations by Procedure
Dysmorp
hology
Non-Inva
sive b
lood pressu
re
Calorim
etry
Simplifi
ed IP
GTTDEX
AX-Ray
Open-field
Modified SH
IRPA
Grip-St
rength
Rotarod
Acoustic S
tartle
&PPI
Hot Plat
e
Indirect
ophthalmosco
py
Slit La
mp
Clinica
l Chem
istry
Haemato
logy
FACs A
nalysis
Immunoglo
bulin
Heart w
eight/ti
bia len
gth
Fasted
Clinica
l Chem
istry
Body Weig
ht0
10
20
30
40
50
60
70
80
90
100
![Page 17: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/17.jpg)
An International Centre for Mouse Genetics
EUROPHENOME (Gene Search)
![Page 18: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/18.jpg)
An International Centre for Mouse Genetics www.europhenome.org
![Page 19: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/19.jpg)
An International Centre for Mouse Genetics
![Page 20: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/20.jpg)
An International Centre for Mouse Genetics
![Page 21: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/21.jpg)
An International Centre for Mouse Genetics
![Page 22: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/22.jpg)
An International Centre for Mouse Genetics
![Page 23: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/23.jpg)
An International Centre for Mouse Genetics
![Page 24: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/24.jpg)
An International Centre for Mouse Genetics
![Page 25: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/25.jpg)
An International Centre for Mouse Genetics
PHENOTYPE SEARCH
![Page 26: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/26.jpg)
An International Centre for Mouse Genetics
![Page 27: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/27.jpg)
An International Centre for Mouse Genetics
![Page 28: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/28.jpg)
An International Centre for Mouse Genetics
![Page 29: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/29.jpg)
An International Centre for Mouse Genetics
![Page 30: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/30.jpg)
An International Centre for Mouse Genetics
![Page 31: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/31.jpg)
An International Centre for Mouse Genetics
PHENOMAP
![Page 32: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/32.jpg)
An International Centre for Mouse Genetics
![Page 33: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/33.jpg)
An International Centre for Mouse Genetics
![Page 34: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/34.jpg)
An International Centre for Mouse Genetics
![Page 35: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/35.jpg)
An International Centre for Mouse Genetics
![Page 36: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/36.jpg)
An International Centre for Mouse Genetics
![Page 37: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/37.jpg)
An International Centre for Mouse Genetics
![Page 38: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/38.jpg)
An International Centre for Mouse Genetics
![Page 39: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/39.jpg)
An International Centre for Mouse Genetics
XRAYS
![Page 40: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/40.jpg)
An International Centre for Mouse Genetics
![Page 41: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/41.jpg)
An International Centre for Mouse Genetics
![Page 42: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/42.jpg)
An International Centre for Mouse Genetics
SANGER MOUSE PORTAL
![Page 43: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/43.jpg)
An International Centre for Mouse Genetics
http://www.sanger.ac.uk/mouseportal
![Page 44: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/44.jpg)
An International Centre for Mouse Genetics
![Page 45: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/45.jpg)
An International Centre for Mouse Genetics
International Mouse Phenotyping Consortium (IMPC)
![Page 46: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/46.jpg)
An International Centre for Mouse Genetics
IMPC 22 Academic, Government Institutes
MRC Harwell (Steve Brown, current Chair Steering Comm.; Tom Weaver)
Sanger Institute (Allan Bradley, Dave Adams, Karen Kennedy)
NIH KOMP2 BASH, Baylor (Monica Justice) DTCC (UC Davis (Kent Lloyd), TCP,
Charles River, Children’s Hospital Oakland RI)
Jackson Lab (Karen Svenson) Toronto Centre for Phenogenomics (Colin
McKerlie) Helmholtz Zentrum Munich (Martin Hrabe de
Angelis) Institut Clinique de la Souris (Yann Herault) Australian Phenomics Network (Adrienne
McKenzie) RIKEN BioResource Center (Yuichi Obata) MARC (Xiang Gao) CNR (Glauco Toccinni Valentini) EBI (Paul Flicek)
Secretariat (Mark Moore, Executive Director; Joerg Rossbacher)
FUNDERS MRC (Nathan Richardson, Clare
Newland) NIH (Jane Peterson, Eric Green, Jim
Battey, Colin Fletcher, Martin Guyer) Wellcome Trust (Michael Dunn, Clare
McVicker) Infrafrontier (Martin Hrabe de
Angelis) Genome Canada (Cindy Bell) European Commission (Observer
status) Canadian Institutes of Health
Research, CIHR (Jane Aubin)
![Page 47: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/47.jpg)
An International Centre for Mouse Genetics
What is IMPReSS?
• IMPReSS: International Mouse Phenotyping Resource of Standardised Screens
• Launched Tue 13th March 2012• The successor of EMPReSS - Inherits historical Pipelines, adds IMPC
Pipeline• New architecture, new site, plus some more features
![Page 48: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/48.jpg)
An International Centre for Mouse Genetics
IMPReSS – IMPC Pipeline
• Adult pipeline agree and embryonic pipeline in development
![Page 49: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/49.jpg)
An International Centre for Mouse Genetics
Key Concepts: 3Ps
Pipeline
Procedure
MeasuredParameter
MetadataParameter
*:*
*:*
3Ps have unique identifiers, Keys, e.g: IMPC_001_001_005_001
contains
contains
![Page 50: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/50.jpg)
An International Centre for Mouse Genetics
Ontology Associations
• Ontology Associations• Structured, controlled vocabulary used worldwide by scientists to
describe phenotypes and beyond• Various Collections but MP is popular• Predefined option choices for high throughput ontology annotation
• Procedure: Open Field– Measured Parameter: Distance Travelled
» MP:0001399 - Hyperactivity » MP:0001402 - Hypoactivity » MP:0003313 - Abnormal locomotor activation
• Can compare baselines against mutants by ontologies associated with the mice to identify phenotypes and variations and can also QC submitted data
![Page 51: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/51.jpg)
An International Centre for Mouse GeneticsHomepage http://www.mousephenotype.org/impress
![Page 52: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/52.jpg)
An International Centre for Mouse Genetics
![Page 53: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/53.jpg)
An International Centre for Mouse Genetics
![Page 54: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/54.jpg)
An International Centre for Mouse Genetics
![Page 55: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/55.jpg)
An International Centre for Mouse Genetics
![Page 56: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/56.jpg)
An International Centre for Mouse Genetics
![Page 57: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/57.jpg)
An International Centre for Mouse Genetics
![Page 58: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/58.jpg)
An International Centre for Mouse Genetics
![Page 59: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/59.jpg)
An International Centre for Mouse Genetics
MPI2
Component Owner Partners
Project Management, Reporting and Community Outreach
EBI Harwell/Sanger
Tracking Database Sanger Harwell
SOP and Pheno-DCC Harwell Sanger
Annotation Pipelines Harwell Sanger/EBI
Central Data Archive EBI Sanger/Harwell
Web Portal EBI Sanger/Harwell
![Page 60: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/60.jpg)
An International Centre for Mouse Genetics
New Homepage for IMPC Portalhttp://www.mousephenotype.org/
![Page 61: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/61.jpg)
An International Centre for Mouse Genetics
Basic Search Functionality added
• Displays subset of iMITS data• Many planned improvements ahead
• download entire gene list• register for gene of interest• will link to IMPC phenotype data as available
![Page 62: Mining phenotype databases to identify mouse models of clinical relevance](https://reader035.vdocuments.mx/reader035/viewer/2022062810/56815e7e550346895dcd0a9f/html5/thumbnails/62.jpg)
An International Centre for Mouse Genetics