1. An International Centre for Mouse Genetics MINING PHENOTYPE DATABASES TO IDENTIFY MOUSE MODELS OF CLINICAL RELEVANCE Michelle Simon and Ann-Marie Mallon

2. An International Centre for Mouse Genetics Introduction Introduction – EUMODIC EuroPhenome (www.europhenome.org)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.

3. 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

4. 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

5. An International Centre for Mouse Genetics EuroPhenome Data Capture SOPs DefinitionDefining data StandardsData Capture in LIMSData Export to Centralised DBValidation and QC

6. An International Centre for Mouse Genetics EMPRESS (EUROPEAN MOUSE PHENOTYPING RESOURCE OF STANDARDISED SCREENS)

7. 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)

8. An International Centre for Mouse Genetics EMPRESS http://empress.har.mrc.ac.uk/ Comprehensive database of standardised phenotyping protocols. Search procedures

9. An International Centre for Mouse Genetics EMPRESS Four different phenotyping pipelines Procedures

10. An International Centre for Mouse Genetics EMPReSS Unique Empress Identifier Different Parameters Measurement types and increments Ontology Annotation - Mammalian Phenotype

11. An International Centre for Mouse Genetics EMPReSS SLIM, Primary Phenotyping Screen 21 different procedures

12. An International Centre for Mouse Genetics Phenotype Data Capture Automatic data annotation of significant phenodeviants with MP ontology terms

13. 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 Annotation Database

14. An International Centre for Mouse Genetics EUROPHENOME STATISTICS Number of Lines

15. An International Centre for Mouse Genetics Data in Europhenome 502Lines 2,505 30,276 Mice

16. An International Centre for Mouse Genetics Number of Lines with significant annotations by Procedure

17. An International Centre for Mouse Genetics EUROPHENOME (Gene Search)

18. An International Centre for Mouse Genetics www.europhenome.org

19. An International Centre for Mouse Genetics

25. PHENOTYPE SEARCH

26. An International Centre for Mouse Genetics

31. PHENOMAP

32. An International Centre for Mouse Genetics

39. XRAYS

40. An International Centre for Mouse Genetics

42. SANGER MOUSE PORTAL

43. An International Centre for Mouse Genetics http://www.sanger.ac.uk/mouseportal

44. An International Centre for Mouse Genetics

45. International Mouse Phenotyping Consortium (IMPC)

46. 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)

47. An International Centre for Mouse Genetics What is IMPReSS? IMPReSS: International Mouse Phenotyping Resource of Standardised Screens Launched Tue 13 th March 2012 The successor of EMPReSS - Inherits historical Pipelines, adds IMPC Pipeline New architecture, new site, plus some more features

48. An International Centre for Mouse Genetics IMPReSS – IMPC Pipeline Adult pipeline agree and embryonic pipeline in development

49. 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

50. An International Centre for Mouse Genetics 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

51. An International Centre for Mouse Genetics Homepage http://www.mousephenotype.org/impress

52. An International Centre for Mouse Genetics

59. MPI2 ComponentOwnerPartners Project Management, Reporting and Community Outreach EBIHarwell/Sanger Tracking DatabaseSangerHarwell SOP and Pheno-DCCHarwellSanger Annotation PipelinesHarwellSanger/EBI Central Data ArchiveEBISanger/Harwell Web PortalEBISanger/Harwell

60. An International Centre for Mouse Genetics New Homepage for IMPC Portal http://www.mousephenotype.org/

61. 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

62. An International Centre for Mouse Genetics