Genomics England Clinical Interpretation Partnership Friday 5 Dec 2014 Prof Mark Caulﬁeld FMedSci Chief Scien5st The Genomics England Clinical Interpretation Partnership What will be available? Rare Inherited Diseases •  7000 disorders-‐ 50% no genomic diagnosis -‐ Pilot on 110 phenotypes •  Detailed & genomically primed phenotyping •  Diagnos5c tests •  Human Phenotype Ontology •  Disease progression •  Disease nomina5on by clinicians from Genomic Medicine Centres and GeCIP domains •  GeCIP domains advise on disease selec5on & data model •  RD Connect/NIHR BioResource •  Phenotype collec5on adapts •  Best use of WGS •  Rare Disease registry Cancer •  Lung, breast, colon, prostate, ovary and, Chronic Lymphocy5c Leukaemia •  Rare and Childhood Cancers, unknown primary •  75X for soma5c, 30X germline •  700 enrolled – 46% pass QC for Sequencing •  Disease nomina5on by clinicians from Genomic Medicine Centres and GeCIP domains •  GeCIP domains advise on disease selec5on & data model •  Best use and priori5sa5on of WGS Stra5ﬁed Healthcare •  Focus 4 – Colon cancer, Britroc-‐ Ovarian cancer •  TRACER X-‐ Lung cancer. UK CLL consor5um Cancer Data Model Generic ﬁelds (all tumour-‐types): •  Sample data: ﬁxa5on, DNA extrac5on •  Iden5ﬁers •  Tumour data: TNM, morphology, topography, margins •  Clinical episode data: clinical evalua5on, inves5ga5on (all types), treatment (all types), follow-‐up evalua5ons •  Molecular and Digital Pathology & genomic tests Tumour-‐type speciﬁc ﬁelds: •  Sub-‐type, presenta5on, tumour markers, risk factors (including family history), •  Rich dataset capturing lifecourse data of pa5ent and tumour •  Predominantly via rou5ne cancer registry data collec5on (COSD, SACT, RTDS) •  Working with NCRS/NCIN to op5mise data capture Pathogens •  Stra5fying response, minimising adverse events and tracking outbreaks •  M. Tuberculosis resistance and epidemiology •  Hepa55s C genotype selects therapy •  HIV –Treatment for life and resistance tes5ng is in the care pathway. •  Extreme human response to sepsis •  Interna5onal linked datasets Multi-omics Repository In rare disease and cancer NHSE is funding plasma and serum sampling enabling poten5al for •  RNA transcriptomics, micro RNAs •  Epigene5cs, Proteomics and metabolomics In cancer NHSE is funding sample capture •  Cell free circula5ng DNA (liquid biopsy) •  Sequen5al biopsies & WGS (trials) We need to raise funds for: •  Tumour sampling for transcriptomics, expression and other omics •  Circula5ng Tumour cells •  Cancer Cell Lines for organoids for drug sensi5vity, single cell physiomics or func5onal genomics Genomics England – The main programme NHS Genomic Medicine Centres Rare diseases, cancers and pathogens Broad consent, characteris5cs, molecular pathology and samples DNA & mul5-‐omics Repository Refreshable idenEﬁable Clinical Data Life-‐course registry Primary Care Hospital episodes Cancer Registries Rare Disease Registries Infec5ous Disease Mortality data Pa5ent entry Oxford Big Data NHS Sequencing Centre Wellcome Trust £27m Linked to anonymised Whole Genome Sequence MRC £24m Research Data Infrastructure (GeCIP) SequenEal builds of pseudonymised data and WGS Safe haven-‐ users work within Fire wall Pa5ent data stays in safe haven Only processed results pass outside Clinicians & Academics Training & capacity Industry Annota5on & QC Scien5sts & SMEs Product comparison Feedback to the NHS •  Simple accessible and meaningful for pa5ents •  Dynamic serial repor5ng-‐ evolving ﬁndings •  Known Pathogenic and ac5onable •  Expected Pathogenic •  Secondary looked for ﬁndings-‐ cancers/FH •  E.g. Lynch syndrome, BRCA1/2, MEN, VHL •  Carrier states of reproduc5ve importance •  Raw reads and annota5on accessible to NHS Systema5c approach to valida5on •  Pa5ents can request annotated VCFs and BAM ﬁles from Genomics England The Genomics England Clinical Interpretation Partnership Why do this? How is it structured? Why do we need a Clinical Interpretation Partnership? The standard way The GeCIP way Start 2014 17 yrs ?3 yrs Securing Patient Benefit Genomics England Clinical Interpretation Partnership expectations •  •  •  •  •  •  •  •  •  Drive up the ﬁdelity of clinical interpreta5on of WGS UK –led self-‐organised into domains Partnership with researchers, the NHS and Trainees with skills. Can bring interna5onal collaborators Possible forma5on of a precompe55ve consor5um of a limited number of industry partners. All data generated contributes to the Genomics England Dataset and are available to all. Designed to accelerate academic/industry partnership and development of diagnos5cs and therapies. Recognises that to get to a therapy will require signiﬁcant addi5onal R&D which we aim to s5mulate here in the UK. IP owned by Genomics England but freely licensed Genomics England Clinical Interpretation Partnership Rare Disease, Cancer and Infection Domains Organised in Disease Domains Key functions and outputs UK led - steering group Appoint domain leader & sub-groups Genomics England Chief Scientist’s Team Oversight, informatics and logistics for the programme Multiple phenotypic sub-groups Deeper phenotyping & extend programme Functional characterisation Multi-omics Single cell or model functional studies RNA, epigenetics, proteomics Analysts and Bio-informaticians Novel analytic approaches Interpretation - NHS and PHE teams and Researchers Highest fidelity dynamic reporting system Integrated Multi-Disciplinary Team Training - HEE/GECIP trainees Genomic Medicine Academy Precompetitive industry partners Academic/Industry Collaboration Training and Capacity •  Training Director per domain •  Training embassy – all funders can use •  700 person years of training between now and the end of 2017 •  Specialist genetics, pathology and specialist clinical workforce in Genomic Medicine •  Increase in specialised scientific training fellows funded over 3/5 years: •  Molecular Pathology including Infections and Pathogens •  Genetics / genomics •  Bioinformatics •  Masters in Genomic Medicine, Bioinformatics for Genomics www.hee.nhs.uk www.hee.nhs.uk The Genomics England Clinical Interpretation Partnership Working with industry or Interna5onal collaborators Industry Partnership •  This is not the mechanism for industry to apply to work with the 100,000 Genomes Project •  It is possible by a separate process that industry may work with or within GeCIP domains •  Pharma, SMEs, Diagnos5c and Therapeu5c Innova5on •  Precompe55ve consor5a •  Private embassy •  Stra5ﬁed Medicine [email protected] International Partnership •  Global Alliance for Genomic Health •  Veterans Administration •  Large cohort (1M), contract let for 5000 WGS •  US Integrated Healthcare Systems •  Scripps – Wellderly Study sequenced 2000 volunteers to study lifestyle •  Inova Health – aims to provide worlds largest WGS database, 1500 completed thus far •  Clinical Research programmes •  •  •  •  •  •  •  •  •  Oxford 500 WGS, DDD (Sanger) up to 12,000 children (mainly exomes) International Cancer Genome Consortium Seattle – 100K WGS –Lee Hood Care for Rare and Genome Canada UPenn - Prenatal St Jude and the Moffit Cancer Centres Middle Eastern programmes in Saudi, Abu Dhabi and Quatar Chan Shoon-Shiong Foundation Personal Genome Project – aims for 100,000, all open data Genomics England Clinical Interpretation Partnership What happens about Intellectual Property? Intellectual property •  The UK Taxpayer is providing most of the funds •  Genomics England owns the clinical data and the WGS and all results generated by GeCIP •  We will readily license any inven5on back to you •  Favourable terms •  You will need to ensure you have brought all your co-‐inventors with you •  Encourages open innova5on Genomics England Clinical Interpretation Partnership How do I access the data? 100,000 Genomes Project Access Review Policy •  Independent Commijee Chair and Members in the majority •  Input from internal Science, Data Access, Ethics Advisory Commijee •  Pa5ent representa5ves •  Access to your domain •  Crosscukng domains •  Broad Access providing in accordance with informed consent •  Access monitored Data Access Application and Review Process Genomics England Clinical Interpretation Partnership What are the timelines? GeCIP Timeline ApplicaEon Phase 1st quarter of 2015 Access to Data 2nd quarter of 2015 Assessment of domains End of Year 1 •  Applica5ons close on 26th January 2015 -‐ Forma5on of introductory GeCIP Domains •  3 months later (March 2015) -‐ Detailed research plan •  Apply for funding •  Access to GeCIP domain embassy -‐ dependant on pa5ents enrolled and sequenced •  •  First data release Shaping op5mal domain embassy – new speciﬁca5ons or func5onality •  Assessments on the func5onality, enhanced feedback and added value of GeCIP domains (GeCIP Board and Oﬃce of the Chief Scien5st) Future calls for interest •  Welcoming proposals for new domains/applica5ons to engage in established domains Summer 2015-‐2016 Genomics England •  100,000 WGS on NHS pa5ents and pathogens •  Aware of the challenges •  Working with NHS, academics and industry to drive Genomic Medicine into the NHS •  Support that with educa5on •  Leave a legacy of NGS Centres, sample pipeline and biorepository, large-‐scale data store that makes this usable by the NHS •  New diagnos5cs and therapies and opportuni5es for pa5ents •  By end of 2017 Genomics England – who are we? •  Oﬃcers: Sir John Chisholm (Execu5ve Chair) •  Mark Caulﬁeld (Chief Scien5st), Nick Maltby (Company Secretary), Jim Davies (Informa5cs), Viv Parry (Outreach), Graham Colbert (COO) •  Board: Prof Dame Sally Davies (CMO), Kevin Dean (Cisco), Prof Sir John Bell, Jon Symonds (Audit), Prof Sir Malcom Grant (NHSE), Prof Dame Kay Davies (GeCIP), Viv Parry (Outreach) •  Advisory CommiXees: •  Science: Sir John Bell, IT: Kevin Dean and Ethics: Mike Parker Team members Science Tom Fowler, Jeanna Mahon-‐Pearson, Mina Ryten, Laura Riley, Mario Black, Nora Wong, Clare Turnbull InformaEcs Jim Davies, Tim Hubbard, Augusto Rendon, Majhew Parker, Andrew Devereau, Katherine Smith, David Brown Thanks Cambridge, UCLH, GOSH, Moorﬁelds, Newcastle, Manchester, Guys and St Thomas’s, Oxford, Liverpool, Sheﬃeld, Leeds, Birmingham, Royal Marsden, Southampton, UK CLL Consor5um, CRUK, RCPath, NHSE, DoH, Biobank UK, Sanger, EBI, KCL, UCL and QMUL Questions? [email protected] #100KGP