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The MRC DNA Bank: the story so far. ESF Workshop on Biobanks: practical, ethical and legal aspects. Uppsala 13 September 2002. Mission s tatement The MRC's mission is set out in its Royal Charter :

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The mrc dna bank the story so far l.jpg

The MRC DNA Bank:the story so far

ESF Workshop on Biobanks:

practical, ethical and legal aspects

Uppsala 13 September 2002


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  • Mission statement

  • The MRC's mission is set out in its Royal Charter:

  • To encourage and support high-quality research with the aim of maintaining and improving human health

  • To train skilled people, and to advance and disseminate knowledge and technology with the aim of meeting national needs in terms of health, quality of life and economic competitiveness

  • To promote public engagement with medical research


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Medical Research Council

50 Institutes

and Units

UK Human

Genome

Mapping

Project

Resource Centre:

an MRC Unit with three divisions


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Unit

Divisions

UK HGMP RC

www.hgmp.mrc.ac.uk

Research

Bioinformatics

MRC geneservice

  • Functional

  • genomics

  • Software

  • development

  • Research products

  • and services


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MRC geneservice mission

  • To develop and provide at cost-recovery innovative functional genomic products and contract research services

  • for the European academic and commercial research community

  • to improve human health


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Objectives

Non-restricted access

Unique genomic resources

Enabling technologies

Cost recovery

Value for money

Invest in infrastructure

Offering

Products and services

Functional genomics

Translational research

Market

Academic and commercial

Public/private partnering

Key Points


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Business Model

  • Short term

    • Products and contract research

    • R&D via collaborations/grants

    • Strengthen products and service offering

    • Increase volumes/market share

    • Full cost recovery by 2006

  • Long term

    • Growth in internal research

    • Partnering/Joint Ventures

    • Develop IP portfolio


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Organisation

  • Moved to Babraham: July 2001

    • Non-profit government organization

    • Bioinformatics and R&D support at Hinxton

  • Commercial infrastructure

    • 32 staff

    • Operations/IT/Finance/Business Development

Cam

Ba

Hi


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Recent highlights

  • Commercial Development

    • Business Plan: Feb 01

    • Premises at Babraham: July 01

    • Commercial team in place: Dec 01

    • MRC Board accepts budget and business strategy: Apr 02

    • MRC geneservice launched: May 02


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Recent Highlights

  • Product and Service development

    RNA Service

    1st academic and commercial Affymetrix Microarray service provider in UK: Dec 01

    1st commercial deal: May 02

    Quantitative PCR validation of microarray results: July 02

    Cloning Service

    Pilot production line of expression ready clone (mouse cancer ORF set): Aug 02

    DNA Service

    1st commercial SNP genotypng deal: April 02

    National DNA banking award: July 02

    Reagents

    C. elegans RNAi clones, ScFv library, RIKEN FL mouse clones, MGC FL Human cDNAs


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Global distribution

> 11,000 users in

> 40 countries

Web ordering system

Online product description

3 day turn-around


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DNA Service

  • DNA extraction

  • Fresh frozen whole/separated blood

  • Mutation Detection and SNP Validation

  • PSQ; WAVE HPLC; sequencing

  • Genetic studies

    • Linkage and association studies

    • HTP microsatellite & SNP typing pipeline

      Provide access to

      • Technology and analysis tools

      • Training

  • Genetics network

    • 18 collaborations

    • Immunology, cardio-vascular, neurological, cancer studies


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    Genotyping platform - TaqMan

    Liquid handling Water bath PCR Acquire data: analyse

    Current daily throughput

    1 FTE

    100 x 384-well plates = 38K assays

    95% call rate (variable DNA quality)

    100% concordance


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    R

    R

    R

    R

    Laboratory Information Management System

    4R

    replicating re-arraying

    recording reporting

    • Allows users to create a system to track a laboratory process

    • Allows users to define annotations for samples

    • Provides a repository for results

    • Provides reports

    • Provides an audit trail

    • Maintains need-to-know security


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    DNA Service: work in progress

    • Planning and starting to build a DNA bank


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    Milestones on road to DNA Bank

    • October 2000: MRC funds 13 collections

    • December 2000: MRC calls for proposals for a UK network for DNA sample banking and genotyping

    • May 2001: MRC workshop on its initiative

    • July 2001: MRCg et al submit proposal

    • July 2002: MRC selects MRC geneservice as a DNA banker


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    13 collections funded by MRC in October 2000

    • Age-related macular degeneration families

    • Colorectal cancer cases, relatives, matched controls

    • Hypertension nk

    • Parkinson’s disease nk

    • Multiple sclerosis cohort

    • Asthma and eczema family collection

    • Acute coronary event families

    • Type 2 diabetes nuclear familial

    • Acute leukaemia MRC clinical trials patients

    • Unipolar depression case control study

    • Glomerulonephritis cases

    • Breast cancer affected sib pairs

    • Late onset Alzheimer’s disease case control study

    • 40K samples being collected

    • Each applicant already has appropriate ethical approval

    • Grant conditions require collections to be placed in MRC DNA banking centres

    • Most collectors have well-supported labs and international reputations


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    MRC call for UK network: Dec 2000

    • The MRC

    • recognises importance of genetic epidemiology in the post-genome era

    • announces its aim of establishing a network of centres

    • envisages network as part of the Biobank infrastructure

    • the network will:

    • have custody of large DNA collections

    • manage the collections

    • integrate data systems across the network

    • common standards and practice

    • pilot high throughput genotyping

    • Network resources to be made available to UK scientists


    Mrc call for uk network l.jpg
    MRC call for UK network

    • Scope of network

    • initial storage capacity: 100,000 samples

    • potential to expand to manage other studies funded by MRC - or others with cost recovery

    • “geographically clustered” groups encouraged to form consortia

    • long-term national HT genotyping service

    • Assessment of bids

    • Two stage review to differ from normal peer review process:

    • 1. consortia to express interest: experts were to select a short-list

    • 2. selected consortia to submit work plans that

    •  ensure “users” needs are met - including ready access to samples

    •  demonstrate commitment of hosts


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    Expression of interest from Cambridge

    • Summary of expertise available in Cambridge

    • and of experience with large projects

    • Submitted from

    • 3 MRC units in Cambridge

    • 11 University of Cambridge departments (including two MRC 13 collector PIs)


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    Cambridge application for MRC DNA Bank: July 2001

    Institute of Public Health

    + other Cambridge groups

    including Sanger Institute


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    Overall bank organisation

    DoH/MRC/ MRC COREC

    WT DNA

    BANKERS

    Materials Operations

    and Methods Committee

    Group

    OPERATIONS


    Operations organisation l.jpg
    Operations organisation

    IPH UK HGMP RC ECACC

    Operations

    Systems and Cell and Genotyping Services

    Data Group DNA Group Group Research

    Group


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    Work flow

    DNA Bankers

    blood samples

    Blood DNA Storage Retrieval Tests Analysis

    Archive WGA QC/QA

    Lines Operations

    : automated steps (to be introduced one at a time)


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    MRC DNA BANKING AND GENOTYPING INITIATIVE

    Combined Application: Plan of Work and budgets

    ·MRC geneservice

    ·Centre for Integrated Genomic Medical Research

    ·European Collection of Cell Cultures

    MRC selects centres: March 2002


    Mrc dna banking network l.jpg
    MRC DNABankingNetwork


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    Combined application: June 2002

    The MRC DNA Bank service will comprise:

    ·organising with the collectors the despatch of samples from their subjects

    ·receipt of subjects’ blood or DNA samples (or receipt of samples from ECACC)

    ·extraction of DNA

    ·housing of DNA

     standard DNA concentration and DNA quality determination


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    Questionnaire to collectors

    • Questionnaire probed status of collections

    • - all at different stages: some not started

    • - some collectors query the custody status of samples

    • - different protocols


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    Current status of DNA Bank

    • Final negotiations are underway

    • MRCg and CIMR will use existing DNA extraction facilities

    • Standardised sample storage systems will be used

    • ECACC and CIMR will seek to improve EBV immortalisation

    • MRCg will develop and implement WGA

    • MRCg and CIMR will improve aspects of SNP typing

    • MRCg hopes to acquire an advanced storage system

    • Also MRC is to support a distinct collectors’ consortium


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    Matters arising

    • Should a national DNA bank be set up before or after collections have been funded?

    • Should a strategic national project conceived centrally be selected from proposals conceived locally?

    • Is it realistic to expect ‘geographical clusters’ to form in preference to ‘expedient clusters’?

    • Is there an overwhelming need for a ‘network’?

    • In what ways might the network be part of the Biobank infrastructure?

    • How can we overcome the reluctance of collectors to share even an aliquot of their sample plus associated phenotypic/clinical data?


    Should a national dna bank be set up before or after collections have been funded l.jpg
    Should a national DNA bank be set up before or after collections have been funded?

    • Organisational factors

    • If custody of samples and data sharing is not readily resolved, then fund collectors first

    • Scientific factors

    • Our data provide evidence that HT genotyping requires consistent quality DNA. As [DNA]/rx falls with UHT genotyping, we believe this will become an absolute requirement for high call rates and concordance


    Slide32 l.jpg
    Should a strategic national project conceived centrally be selected from proposals conceived locally?

    • This depends on the extent to which the project will directly innovate or discover: the more the amount of innovation / discovery anticipated, the greater the need for local proposals. A danger exists that local proposals may second-guess central conceptions so that the best guess wins.

    • NB: the distinction between ‘vertical’ and ‘horizontal’ projects is useful post hoc


    Is it realistic to expect geographical clusters to form in preference to expedient clusters l.jpg
    Is it realistic to expect ‘geographical clusters’ to form in preference to ‘expedient clusters’?

    • Competitive bidding for funds will tend to favour the creation of clusters (i.e. consortia) that most readily create the strongest possible bid on scientific grounds. The Cambridge bid was mainly geographic – but not in the sense MRC intended. The non-Cambridge applicant is located ~200 km away.


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    Is there an overwhelming need for a ‘network’? form in preference to ‘expedient clusters’?

    • The trend in large pharma genotyping projects is toward out-sourcing and toward complete centralisation. This is for reasons of capital/labour costs and data quality respectively.


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    In what ways might the network be part of the Biobank infrastructure?

    • The network will achieve harmonisation of procedures and ensure full interactivity of data systems. It is essentially a collaboration. This may meet some of the needs of Biobank.

    • We are confident the MRC geneservice DNA bank will have the experience, processes and equipment needed to satisfy Biobank – and others.


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    How can we overcome the reluctance of collectors to share even an aliquot of their sample plus associated phenotypic/clinical data?

    • There has to be a quid pro quo.

    • Well-supported collectors are more independent in their operations than less well-supported collectors. For the latter, a bank network has more to offer. One may predict that in future collectors – including the MRC 13 – will all understand the virtues of a division of labour.


    Acknowledgements l.jpg
    Acknowledgements even an aliquot of their sample plus associated phenotypic/clinical data?

    • Nick Day; Doug Easton - IPH Cambridge

    • David Lewis; Bryan Bolton - ECACC

    • Bill Ollier; Jane Worthington - CIMR Manchester

    • Duncan Campbell; Tom Weaver - UK HGMP / MRCg