An International Centre for Mouse Genetics EuroPhenome and the International Mouse Phenotyping Consortium John Hancock MRC Harwell

An International Centre for Mouse Genetics “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

An International Centre for Mouse Genetics

EuroPhenome - Data Capture MIMPP-compliant data files (XML)MIMPP-compliant data files (XML) Nightly XML file upload from phenotyping centres Nightly XML file upload from phenotyping centres Validation with EMPReSS e.g. Parameters/units/bounds Validation with EMPReSS e.g. Parameters/units/bounds Validation

An International Centre for Mouse Genetics EuroPhenome

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 1 st 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 Detailed Descriptions Baseline Data Mutant Data Protocols Need Efforts To Facilitate The Linking Of These Data Sets

An International Centre for Mouse Genetics Interphenome (MPDIC) Consortium Mammalian Genome 18, (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 DISEASE Phenotypic Attributes HumanHuman MouseMouse PHENOTYPING Phenotypic Measures Interpreter

An International Centre for Mouse Genetics Thanks To… Ann-Marie Mallon Andy Blake Simon Greenaway Tim Beck Hugh Morgan Octavio Espinosa Georgios Gkoutos Eain Green Joe Weekes Paul Schofield Christoph Lengger Hiroshi Masuya EUMORPHIA EUMODIC The Interphenome group CASIMIR MRC and the EU for funding

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 Ear Nose Brain {Part_Of} Sensory Organ Ear Nose Tongue {Is_A} 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 5 Q: increased length Inferred qualitative description Normal value, e.g. from EuroPhenome Long tail MP: 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: people? Need considerable investment