The 100,000 Genomes Project

Dr Cheryl Flanagan

Molecular Pathology Services Project Manager

Rare Disease Day 2017

28th February

Background

The first human genome sequence

• 100,000 Genomes at Millennium Prices - Cost $320

trillion

• 26th June 2000 - Cost $3.2 billion

Cost per genome

Wetterstrand KA. DNA Sequencing Costs: Data from the NHGRI Genome Sequencing Program (GSP) Available at: www.genome.gov/sequencingcostsdata. Accessed [10/10/16]

The 100,000 Genomes Project

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Background

Announced by the former Prime Minister in December 2012

An Olympic Legacy

Genomics England announced by Secretary of State for Health in speech during NHS 65th Anniversary Celebrations, July 2013

13 March 2017

Chief Medical Officer Recommendations

• 2013 - Professor Dame Sally Davies established a Strategic Priorities Working Group for the Project - chaired by Professor David Lomas (UCL)

• Recommended rare diseases, certain cancers, and infections.

• Areas where they believe the introduction of genomic technology will have the greatest benefit for patient health.

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Accessible at https://www.genomicsengland.co.uk/library-and-resources/

Rare disease

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Why make genetic diagnoses?

1. For the patient

• Understand why their condition happened

• More accurate knowledge of how it might develop in future

• Possible treatment avenues

• Contact with others with the same condition

2. For the family

• Predict whether family members will get the condition

• Offer screening/treatment to prevent it

• Reproductive decisions

3. For medical research

Aims:

• Source expert knowledge to establish a final diagnostic grade gene panel (green list) for each disorder that will be used in the classification of genetic variants to aid clinical interpretation of rare disease genomes

• Engage Scientific Community, encourage open debate, and begin to establish consensus on gene panels for rare diseases.

• Standardisation of terms and collection of gene-disease related information, accumulation of reviews over time, and updated releases

Rare disease programme

• Over 200 disorders so far

Data model: describes the clinical information to be collected for each disorder

Disorders nominated by the NHS and academia

Eligibility criteria: describe which patients to recruit

Gene panel: the genes to be analysed first for patients with that disorder

First families diagnosed from the Newcastle BioResource pilot

Leslie Hedley, 57

WGS revealed Mr Hedley’s kidney failure was caused by a particular genetic variant (INF2 mutation). His family is also being tested and their blood pressure can now be effectively controlled by drugs available on the NHS.

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Jessica Wright, aged 4Georgia Walburn-Green, aged 4

First children receive diagnoses (GOSH)

The 100,000 Genomes Project

Four main aims

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1. To bring benefit to NHS

patients

2. To create an ethical and transparent

programme based on consent

3. To enable new scientific

discovery and medical insights

4. To kickstart the development of a

UK genomics industry

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Key Operational Features

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Genomics England - a company wholly owned by the Department of Health

Sequencing 100,000 genomes

Clinical service, major research project and NHS transformation

Focusing on cancer, rare disease (and infection - Public Health England)

Based on consent

Linking phenotypic and medical record data with genome data

13 NHS Genomic Medicine Centres England & NI

Data held in a secure and monitored environment with strictly regulated access for researchers including industry

Genomic medicine education programme lead by Health Education England is embedded in the NHS to upskill the workforce

Over 2000+ scientists and clinicians engaged through disease-based Genomics England Clinical Interpretation Partnership (GeCIPs)

Additional funding through MRC, the Wellcome Trust

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NHS England & NHS Genomic

Medicine Centres

GeCIP Domains

IndustryPartnerships

Genomics England

Illumina

The Principal Partners

How it works

Establishment Phase• Illumina - NHS Genomic Medicine Sequencing Centre in

Hinxton (village in South Cambridge)

• UK Data Infrastructure for Genomic Medicine (with MRC)

• NIHR National Biosample Centre - £24 million state-of-the-art facility to store the samples

• NHS Genomic Medicine Centres (GMC’s) – over 85 Health Trusts, 1,500 NHS Staff (doctors, nurses, pathologists, laboratory staff, genetic counsellors)

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Data CentreNHS Genomic Medicine Sequencing

CentreNIHR Biosample centre

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NHS Genomic Medicine Centres

Responsible for identifying and recruiting participants and for clinical care following results

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• 13 Genomic Medicine Centres covering England

• Devolved Nations Genomic Medicine Centres

• October 2015 Health Minister in the NI, announced £3.3m investment NI Genomic Medicine Centre (NIGMC)

• The creation of the NIGMC is one of the first actions in the NI Rare Diseases Implementation Plan

• Current partners - DoH; HSCB; PHA; PathNet; QUB; UU; PPI; GEL; MRC

• Future partners include DfE; NI Industry; Invest NI; other funders

• Discussion between NI & RoIGovernments

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What are we telling participants?• Information about a

patient’s main condition

• Information about additional ‘serious and actionable’ conditions (optional)

• Carrier status for non affected parents of children with rare disease (optional) Image courtesy of Health Education England

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Additional findings offered in the 100,000 Genomes Project

OPTIONAL!

Requirements:• Reliably detected by genome

sequencing• Curated list of high confidence, high

penetrance variants• Treatable or preventable condition

Other conditions may be added if clinically appropriate and technically feasible

Genomics England Clinical Interpretation Partnership (GeCIP)

• Launched at the Wellcome Trust in June 2014

• Partnership between over 2,000 researchers from academia and the NHS, trainees, plus international collaborators.

• Designed to accelerate academic/industry partnership and development of diagnostics and therapies

• Over 35 topics (domains) of research and most domains cover a single disease or group of diseases and some are wider e.g. epigenomics, health economics and technology.

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Working with the research community

• All data generated contributes to the Genomics England Dataset

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GENE ConsortiumWorking with industry

• 12 companies = the Genomics Expert Network for Enterprises (GENE) Consortium to oversee a year-long Industry Trial

• Aims to identify most effective and secure way to accelerate development of new diagnostics and treatments for patients

• Range from big pharma to small biotech

• Working in a pre-competitive environment

• AbbVie, Alexion, AstraZeneca, Berg, Biogen, Dimension Therapeutics, GSK, Helomics, Roche, Takeda, NGM Biopharmaceuticals, UCB

Health Education England

• 11 University providers of MSc in Genomic Medicine • Aimed at NHS healthcare professionals working in England

• Full/part time study

• Fully funded places available through HEE

• Individual (CPPD) modules available for range of professional backgrounds and groups (e.g. medicine, nursing, healthcare scientists and technologists).

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Genomics Education Programme

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• Online training courses and resources • The fundamentals of genomics• Bioinformatics • The consent process

National Participant Panel

• Includes current participants, quarterly meetings

• Members sit on key committees including the Data Access Review Committee, GeCIP Board, Ethics Advisory Committee

• Produce and input in materials e.g. flyers, leaflets, animations

https://www.genomicsengland.co.uk/about-genomics-england/how-we-work/patient-and-public-involvement/

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Project’s progress so far

• Sequenced over 26,000 whole genomes, with over 19,000 in the datacentre.

• Protocols, standards and data infrastructure that are being developed will ensure frontline clinicians can make the most of the knowledge that genomics provides, for patients now and in the future.

• An automated reporting pipeline has been built, and results are now being returned to clinical teams across the NHS to use in patient care.

http://www.genomicsengland.co.uk/updates/

Building the future of genomic medicine• 100,000 WGS on NHS patients and pathogens

• Concentrating the UK Genomics Knowledgebase in one location

• The NHS, academics and industry partnerships at the outset to drive Genomic Medicine into the NHS and create wealth

• Building the human capacity and capability

• Key international partnerships to add value

• Leave a legacy of NGS Centres, sample pipeline and biorepository, large-scale data store that makes this usable by the NHS

• New diagnostics and therapies and opportunities for patients

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