Kevin Dean Digital Health Assembly 2015
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Transcript of Kevin Dean Digital Health Assembly 2015
www.genomicsengland.co.uk
The UK 100,000 Genomes Project
February 2015
2
The 100,000 Genomes Project
Announced by the Prime Minister in December 2012
An Olympic Legacy
Genomics England announced by Secretary of State for Health in speech during NHS 65th Anniversary CelebraKons, July 2013
3
Why are we doing this?
Three major legacies for pa?ents, the NHS and
the UK economy by 2017
Increased insight and understanding leading to new treatments, devices and diagnos?cs
Thriving private sector investment and commercial acKvity in genomics
Advanced genomic medicine pracKce integrated into the NHS
Plus Posi?ve Public Support
4
Data Type
Large-‐scale Structural Changes
Balanced Transloca?ons
Distant Consanguinity
Uniparental Disomy
Novel / Known Coding Variants
Novel / Known Non-‐coding Variants
Targeted gene sequencing û û û û ü û
SNP+ arrays ûü û ü ü û û Array CGH* ûü û û û û û Exome ûü û ûü ûü ü û Whole Genome ûü ü ü ü ü ü
+ Single NucleoKde Polymorphism * ComparaKve Genomic HybridisaKon
Whole genome sequencing will give us new insights
10,000
100,000
1,000,000
10,000,000
100,000,000
1,000,000,000
10,000,000,000
0 0.5 1 1.5 2 2.5
Genotyping Whole genome 3.3bn bases Both exons and introns Exome
10m bases Exons only
Panels <10m bases
Subset of exons
5
Key Opera?onal Features
} Structurally integrated with Na?onal Health Service
} Selected pa?ent cohort with common cancers and rare inherited diseases
} PaKents posiKvely consent
} Sequencing is undertaken in new state-‐of-‐the-‐art sequencing centre
} Data is held in a safe haven with strictly regulated access to ensure public confidence
} Very large number of scienKsts and clinicians engage through disease based Clinical Interpreta?on Partnerships
} Commercial companies will have defined routes to access
} Common pool of Intellectual Property held by Genomics England and available for licence
} Genomic medicine educa?on programme is mounted in the NHS to prepare for feedback
} Genomics England is consKtuted as a limited company under the governance of a board with a majority of independent directors to enable the agility necessary to lead in this fast developing field
6
Key Pillars for Public Support
} Structurally integrated with Na?onal Health Service
} Selected pa?ent cohort with common cancers and rare inherited diseases
} PaKents posiKvely consent
} Sequencing is undertaken in new state-‐of-‐the-‐art sequencing centre
} Data is held in a safe haven with strictly regulated access to ensure public confidence
} Very large number of scienKsts and clinicians engage through disease based Clinical Interpreta?on Partnerships
} Commercial companies will have defined routes to access
} Common pool of Intellectual Property held by Genomics England and available for licence
} Genomic medicine educa?on programme is mounted in the NHS to prepare for feedback
} Genomics England is consKtuted as a limited company under the governance of a board with a majority of independent directors to enable the agility necessary to lead in this fast developing field
7
Consent & Sample collecKon
DNA extracKon
Biorepository
Sequencing
Variant Calling
InterpretaKon
Feedback to clinician
ValidaKon
Treatment
Clinical Data
To complete the Treatment Cycle for just one Pa?ent requires a Complex Chain of Opera?ons involving numerous Specialist Resources
And most of these operaKons have not been designed or opKmised for the purposes of Genomic Medicine. So the task is truly one of iniKaKng a TransformaKon in Medical PracKce, parKcularly relaKng to rouKne use of coordinated data.
8
This Project is far too Big and Complex to be undertaken by a Single Organisa?on
NHSE and GMCs
GeCIPs
Commercial Partnerships
Genomics England
The Principal Partners
Illumina
9
Clinical Partnership • NHS England is responsible for the medical care of 53 million people • In their recent strategy document NHS England have put Genomic Medicine in the centre of their vision of future medical pracKce
• As first step NHS England have run a naKon-‐wide compeKKon to select 11 Genomics Medicine Centres (GMCs) to coordinate and integrate the work of more than 100 Hospital Trusts
o IdenKfying and recruiKng paKents matching the project requirements
o Obtaining informed consent o Obtaining, storing and transporKng blood samples o Obtaining, fixing, storing and transporKng biopsies and resecKons o Where appropriate extracKng tumour cell samples o Providing first dataset necessary for sequencing o Providing clinical dataset necessary for analysis o Receiving and validaKng the clinical feedback o Informing and treaKng the paKents
Consent & Sample collecKon
DNA extracKon
Biorepository
Sequencing
Variant Calling
InterpretaKon
Feedback to clinician
ValidaKon
Treatment
GMC responsibility
• GMCs will be the focal points for coordinaKng the supply of samples and data for their region and receiving the clinical feedback and will be responsible for (amongst other things)
10
Sequencing Partnership • We ran a worldwide compeKKon open to any provider who could demonstrate an ability to provide accurate whole genome sequences
• Chose Illumina as the best demonstrable product, the clearest understanding of the requirement, and the most complete offering
• Signed a Partnership agreement in July 2014 o Illumina invest in a state-‐of-‐the-‐art sequencing centre at Hinxton o Wellcome Trust/Sanger provide the physical infrastructure o Illumina are commifed to working with us to opKmise the genomics medicine cycle
from receipt of the DNA through to interpretaKon and to advise on the protocols in the clinical pathways to maximise the probability of reliable and Kmely results
Consent & Sample collecKon
DNA extracKon
Biorepository
Sequencing
Variant Calling
InterpretaKon
Feedback to clinician
ValidaKon
Treatment
11
Clinical Interpreta?on Partnerships • We ran a world-‐wide compeKKon to test the state-‐of-‐the-‐art in annotaKon and interpretaKon of genomic data
• It is clear that scienKfic and clinical understanding is far from mature • So we have iniKated the creaKon of a network to draw in the best clinical and scienKfic minds from the UK and around the world to access our data and interpret the results
Sample collecKon
DNA extracKon
Biorepository
Sequencing
Variant Calling
InterpretaKon
Feedback to clinician
ValidaKon
Treatment
Work of ~40 disease groups involving upwards of 1000 Clinicians and ScienKsts
The Genomics England Clinical InterpretaKon Partnerships are • Defined by diseases or cross cujng themes. We expect
40+ GeCIPs in all • Each must have a clear and unique focus and be open
to all experts in that field. We expect an average of maybe 50
• Once designated GeCIPs have free access to the data infrastructure and the dataset
• All IP held by Genomics England but available for licence
12
Genomics England specific Responsibili?es
Sequencing Centres
Biorepository
Consent
Clinical Data Samples Samples Samples
Clinician
Genomics England InformaKcs Infrastructure
ScienKfic + Clinical Users
Commercial Users
13
InformaKcs Architecture
Fast Track Feedback Path
Data Handling
Cohort Handling
Variant Calling
+++ +++
M
Clinical Data IdenKty Data
Clinical Data VCFs BAMs • Management • Genomic data
checking • User idenKty
checking • Resource
allocaKon • AcKvity
oversight • Output report
validaKon
Management, QC, IdenKty control, Clinical feedback
GeCIP embassies Commercial embassies
Clinical Feedback Report
From GMCs
From Sequencing Centre
InterpretaKon
14
Commercial Partnerships
Ø For the Pharma industry we are proposing they join a pre-‐compeKKve consorKum and engage in an iniKal trial using a set of 5000 genomes together with appropriate clinical data
Ø For the Biotech industry we will configure more focused datasets for a trial period to give each access to data relevant to their business plan
Ø For the Bio-‐informa?cs and Analy?cs industry we will choose the best performing players to work with us as Plalorm Partners to prove their techniques and tools and provide clinical interpretaKon and services to our research customers
We have segmented the space into three broad categories with a different approach to each
15
But there are many other Important Partnerships
Ø Precursor Rare Disease Programmes: Oxford’s WGS500 project, the Sanger’s Deciphering Developmental Disorders project, and NIHR’s Bioresource Rare Disease project are all precursors which are both providing invaluable learning and also addiKonal input to our dataset
Ø Mul?-‐omics approach to Cancer: we are working with Oxford University’s Chan-‐Soon-‐Shiong Oxford Centre for Molecular Medicine and Nanthealth to opKmise Kssue sample techniques and use mulK-‐omics processes for providing individualised, data driven molecular based medicine
Ø Molecular Pathology: we are working with iniKaKves launched by the MRC and the Royal College of Pathologists to examine improvements in protocols and equipment to enhance quality of DNA, parKcularly for cancer tumours
Ø Longitudinal Clinical Data: our consent protocol permits revisits and data refresh up to 4 Kmes per annum
Ø Circula?ng Tumour Cells: we have a number of partners interested in opKmising techniques for extracKng quality tumour DNA in circulaKon so as to understand progression of cancer
To deliver the ambiKons of this project we are working with other key partners to address numerous related issues. These include
16
Where are we on our plan?
Phase 2 -‐ Pilots
Phase 3a – Main Programme Proving Phase
Phase 3b – Main Programme Running at Volume
Phase 1 Bake-‐offs 0
10000
20000
30000
40000
50000
60000
2014 2015 2016 2017
Genomes per Annum
So what have we achieved so far? Ø Bake-‐offs to establish state-‐of-‐the-‐art Ø Completed vigorously contested compeKKve process resulKng in very producKve
partnership relaKonship with Illumina Ø Pilots almost completed
Ø 2000+ sequences being loaded into data system, plus another 1000 completed (to be delivered later) Ø Extra cancer programme underway to opKmise cancer tumour DNA extracKon Ø Pilot clinical data capture tool operaKng in cancer pilot Ø Many lessons learned concerning opKmising clinical processes
Ø First implementaKon of informaKcs infrastructure went live end of January Ø Clinical data capture tool roll out end of January Ø GMCs mobilisaKon due February Ø GeCIP programme launched, proposals under consideraKon Ø IniKal commercial model being trialled, pharma and biotech companies being signed up Ø Phenomenal world wide interest in the programme
17
What can we expect from this Project? Ø Feedback on perKnent findings – which will get quicker and befer informed as the project progresses
Ø If the paKent opts for it, feedback on any high probability pathogenic findings – again this will develop as the project progresses
Ø Access under strict governance rules to the increasing dataset and a suite of best in class tools
Ø Engagement in a collaboraKve programme with leading scienKfic and clinical experts
Ø Opportunity to share in the publicaKon of findings Ø Possibility to engage in translaKon opportuniKes
with commercial collaborators
PaKents
Research Collaborators
18
What can we expect from this Project? Ø A number of mechanisms to gain access to the dataset and tools under strict governance rules
Ø Engagement with the research collaborators and access to expert clinical and bio-‐informaKcs support
Ø Opportunity to address relevant paKent cohorts both through the Genomics England dataset and through other UK collaboraKons
Ø Opportunity to take up licences to commercialise findings
Ø Possibility of significant advances in diagnosKc markers of geneKc diseases
Ø Possibility of new understanding of mutaKons causing progress of common cancers
Ø Possibility of fresh insights into geneKc markers for common diseases
Commercial Companies
General Public
19
By achieving these we will deliver the legacies
Increased insight and understanding leading to new treatments, devices and diagnos?cs
Thriving private sector investment and commercial acKvity in genomics
Advanced genomic medicine pracKce integrated into the NHS
ü ü ü
Plus Posi?ve Public Support ü
