Ed Millensted - 100,00 Genomes Project
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Presentation by Ed Millensted, Programme Manager, Innovation Agency: 100,000 Genomes Project on Thursday 28 February 2019 at Haydock Park Racecourse
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Ed Millensted - 100,00 Genomes Project
- 1. 100,000 Genomes Project Ed Millensted Programme Manager
- 2. 1 whole set of your genes plus all the DNA between your genes. Copy in almost every cell of your body. Instructions for making, running & repairing. It was thought that the rest of your DNA was rubbish, but now we know better! WGS is a technique used to ‘read’ DNA
- 3. 1. 10 Dec 2012: Prime Minister announced that Government intended to achieve a paradigm shift in way genomics is used across the NHS 2. David Cameron committed the UK to sequencing 100,000 whole human genomes by the end of 2017. 3. The 100,000 Genomes Project focused on sequencing the whole genome of patients with rare inherited diseases and certain cancers 4. Genomics England established to coordinate sample processing and whole genome sequencing.
- 4. 4 A combination of factors: Technological advance eg WGS, wearables Computing power data capture & analytics Cheaper tech Rapid falls in cost Genomics will be a disruptive innovation BUT we will have to make sure that advances can be adopted and delivered rapidly to deliver patient benefit INVENTION EVALUATION ADOPTION DIFFUSION This is our moon shot moment Why the genomic revolution now?
- 5. The Project Journey 22 Dec ‘14: First 11 NHS Genomic Medicine Centres announced Mar ‘15: GMC officially contracted – first two RD patients recruited to main programme Dec’15: Wave Two NHS GMCs announced by Minister George Freeman MP Feb ‘16: Cancer main programme starts following experimental advances Dec ’18 Cancer Project recruitment completes Sep ‘18: RD Project recruitment completes April 2019 Genomic Laboratory Hubs Go Live NHS GMC contract formally ends March ‘19
- 7. • April 2015: Rare Disease recruitment started in 13 centres • Feb 2016: Cancer Main Programme went live, with phased roll-out of Cancer types
- 8. North West Coast GMC 8 20 patient recruitment and sample collection pathways established
- 10. @InnovationNWC Working at the limits of science & practice The greatest challenge of the100,000 Genomes Project has been delivering the future at the same time as devising it - and determining the direction while en route moving at pace. S
- 12. @InnovationNWC Eligible pt identified by clinician Recruitment apt arranged Pt consents to join project Blood/tumour samples obtained DNA extracted Sample data collected Samples + data submitted to bio- repository Clinical data inputted into Open Clinica WGS sequence completed Semi- automated analytics pipeline Result interpreted Result returned to GMC Rare Disease: 1 x blood sample per patient (families) Cancer: 2 x samples per patient (blood + tumour)
- 13. Dec 18 goal reached to sequence 100,000 whole human genomes One in four participants with rare diseases receiving a diagnosis for the first time Potential actionable findings in up to half of cancer patients where there is an opportunity to take part in a clinical trial or to receive a targeted therapy Laid the foundations for a new genomic medicine service Enabled equity of access to genomic testing across England Sequencing: created one of the world’s largest Next Generation Sequencing Centres delivering latest technology and lowest price. Storage: built a multi-petabyte datacentre storing the highest fidelity whole genome DNA sequences with longitudinal clinical data @InnovationNWC
- 14. Bioinformatics: developed one of the world’s few semi-automatic bioinformatics pipelines Faster turnaround of results: 2 years to 30 days Identified need for high quality DNA samples for not only WGS but all genomics to give better results to patients Optimized sample handling and DNA extraction processes e.g. FF vs FFPE Strengthened processes & communication between consenting, surgical, pathology & transport teams Creation of new Genomic Multi-Disciplinary Teams
- 15. o Created new datasets and databases; providing richest possible clinical information o Evolving data manuals: complete & most relevant data collection o New technology; bio-informatics pipeline o Ease of access for clinicians: Combined data from multiple clinical systems into single datasets o Scaled up results: moved from batch to real time result interpretation o Sample data combined with rich clinical data – unique in its kind o GeCIPs – bringing together researchers and clinicians to access genomic information o Reduced cost: WGS now costs around £600 today.
- 16. NHS Genomic Medicine Service Built on existing provision – developing capacity to deliver future technologies + Strong ethical framework & effective consent + Reflecting diversity of the population Workforce development Informatics systems & data store Genomic Medicine Centres & Genomic Clinical Services Industry/ academic/ international partnerships National Whole Genome Sequencing Provision National Network of Genomic Laboratories Genomic Data Interpretation National Test Directory with HEE GEP with Genomics England Strategic Oversight Political oversight: DHSC & Ministerial Board
- 18. Imaging Biochemical & biomarker data Tissue samples Physiological tests Other clinical measurements Genomic sequence data Multi-omics information Eg metabolomics, epigenetics relevant data collected as a series over time Economic, social & population data 21st Century approach individualised and integrated diagnostic and clinical phenotype
- 19. Benefits to Patients Providing Answers Changing Lives
- 20. • Age 3 had speech delay, behavioural problems • Age 11 experiencing severe learning difficulties • Age 18 speech had improved a little, still behavioural problems • Project identified gene alteration in gene ANKRD11, new in Adam • Diagnosis confirmed as KBG syndrome as a result of the project • Provided explanation to Mum and a confirmed diagnosis • Link in with peer and support groups • Possibility that sister may be a carrier but testing confirmed she did not carry the gene
- 21. • Baby born with low muscle tone, unable to breathe by herself, muscles very weak • Diagnosed as profound congenital hypotonia • Parents were pregnant • Project identified variants in gene TBCD, recessive inherited from parents. • Identified as a high recurrent risk in future offspring • Tested for gene during next pregnancy and identified baby was not affected • Reassurance and relief to parents • Generating new scientific and medical understanding
- 22. Earlier prevention of disease Earlier diagnosis More precise diagnosis Earlier treatment Integrating advanced genomics into mainstream NHS Development of personalised medicine
Editor's Notes
- Sequencing a human genome means finding the sequence of someone’s unique 3 billion letters of DNA
- An NHS transformation programme A rare disease is defined by the European Union as one that affects less than 5 in 10,000 of the general population Over 190 rare diseases are currently included in the Project. You can download the list from our website. This list is regularly updated as new diseases are added. When a patient with a rare disease is invited to take part, two of their close relatives are asked as well. This will help doctors analyse the genome. Relatives cannot volunteer for the Project themselves. The background to the odyssey was a recognition that advances in genomics, informatics and analytics brought closer the possibility of more precise diagnosis, alongside personlised and targeted treatments. In 2012 science could see the potential to identify the underlying cause of disease, predict how a person might respond to specific interventions and determine who was at risk of developing an illness. The stumbling block? Nobody had ever tried
- A combination of factors in recent years have allowed the potential of genomics for routine care to finally be delivered
- The challenge: Demand upon NHS services is rising year on year & cancer prevalence is increasing, so new methods are required to improve population health and provide value based health care
- GMCs work across areas of 3 to 5 million people in over 85 NHS trusts. They have been key components of the project: recruiting and consenting patients; providing DNA samples; developing the mechanisms for validating results; and working to feed back results to participants.
- The challenge, described as “laying the track whilst running a train down it at the same time”, was to create the infrastructure for genomic medicine from scratch, whilst also delivering on our objectives. A more traditional model would have seen us build the machinery first and then begin sequencing: the 100,000 Genomes Project did both simultaneously. It was a Project that demanded partnership on an industrial scale – and would never have been delivered without the support of thousands of organisations and individuals.
- Helicopter overview of the project structure
- Open Clinica – RD Strata - cancer Genetic variants identified
- Genomes Project has delivered life-changing results for patients with RD In the past it has taken 13 years and £2 billion to read every letter of human DNA. Today it takes 2 days and costs £600. de-identified format. Previously: Variable access Variable approach Variable quality Data often not linked DNA quality poor Testing not integrated
- Bioinformatics: developed one of the world’s few semi-automatic bioinformatics pipelines – transforming genomics from a “cottage industry” to one suited to a health system at scale. Creation of new Genomic MDTs to review results collectively, enable patients to have access to clinical trials, treatments or different surgical options, and provide clinicians with an educational opportunity.
- We were asked to not only sequence an unprecedented number of whole human genomes, but also to plug this in to the rich health data held by the NHS. GeCIPS - granting them carefully controlled access to our database to power new discoveries in genomic medicine. many of the technologies and services needed to deliver genomic medicine simply didn’t exist – and if we wanted them we would have to build them. One of these technologies was the bioinformatics pipeline, which is critical to ensure processing at the scale in the world’s largest publicly funded health system. This ‘if you can’t buy it, build it’ approach has seen a range of innovations. Work with our sequencing partner, Illumina, for example has acted as a significant catalyst in reducing the costs of sequencing: from billions in 2003 to around £600 today and around £100 in the not too distant future. We have also created a bespoke, multi-petabyte storage environment to cope with the grand challenge of managing a large scale whole genome and clinical dataset.
- NHS England: Policy & strategy, coordinating, contracting & evaluation function with a programme of care & fixed budget Genomic Medicine Centres & Genomic Clinical Services integrated clinical genetics & providing population-based care National Lab Network Building on existing provision and coordinated through 7 regional Genomic Laboratory Hubs to ensure standardisation of approach, comparability of information and quality of service National Test Directory – A single mandated directory of the appropriate genomic tests for specific clinical indications. Based on the best current clinical evidence, peer-reviewed and annually reviewed to ensure the directory keeps pace with technological advance. Whole Genome Sequencing Provision – NHS requirement combined with others Clinical Interpretation – Semi-automated pipeline to speed return of results to maximise clinical utility Workforce development - upskilling of existing staff & ongoing professional engagement in conjunction with Health Education England Industry/ academic/ international partnerships supporting ongoing research & development through clinical care
- The need for Precision medicine is being driven by: Increased understanding of disease Accelerating costs of chronic disease and the burden it is placing on the healthcare systems. Tailoring treatment to those who will benefit most will increase healthcare outcomes and cost effectiveness Identifying those who will predictably experience adverse reactions will increase safety in interventions Comprehensive linked diagnostics to give a full picture of patient Tailored, more-effective therapies for better outcomes Integrated clinical services taking a ‘whole body‘ approach Diagnosis from underlying cause, not sypmtoms Identification of predisposition markers to predict future disease Disease detected 2-8 yrs before onset and before symptoms develop
- 21st Century approach Each patient will have a individualised and integrated diagnostic and clinical phenotype, captured over time This coordinated dataset provides huge opportunities for new insight, analysis, interventions and prognostic possibilities as well as for machine learning
- Age 3 had speech delay, behavioural problems, temper tantrums Age 11 experiencing severe learning difficulties, still poor speech, aggressive
- The 100,000 Genomes Project has been a real innovation – from bioinformatics to computing to storage to research to industry partnership to public engagement. As our learning and dataset grows, so too will our ability to better diagnose and treat an ever expanding number of diseases.