Edinburgh-St Andrews Consortium for Molecular Pathology, Informatics and Genome Sciences

Lead Research Organisation: University of Edinburgh
Department Name: Ctr for Genomic & Experimental Medincine

Abstract

The human genome project and the technological advances that accompanied it, including the recent advent of the "thousand dollar genome" have opened up new possibilities in medicine, including the opportunities for more precise, molecular diagnoses and personalised treatment based on genome information. The technologies are now at a stage where, with appropriate validation and optimisation, they will soon be moved into routine clinical care to accelerate disease diagnosis and improve patient outcomes. However, to introduce this "step-change" in diagnostics and pathology successfully into the clinic, will require the coordinated action of expertise from multiple fields, including the physical sciences, and training of modern-style pathologists to be familiar with multiple advanced technologies.
The Edinburgh-St Andrews Molecular Pathology Node will integrate the proven strengths of the Universities of Edinburgh and St Andrews in molecular pathology and diagnostics (training, development and clinical implementation), image analysis of complex phenotypes and computing, with the breadth of genome medicine and genome sciences experience available within the Universities and NHS Lothian. These strengths include institutes and centres with substantial existing MRC, EPSRC and charitable investment including the MRC Human Genetics Unit, MRC Farr Institute, CRUK Cancer Centre and EPSRC-funded supercomputer and optical imaging facilities.

The main aims of the Node will be: (1) training a new generation of molecular pathologists capable of handling modern genome-analysis-aided approaches to diagnosis and treatment of human disease; (2) developing new tests and clinical applications utilizing the advantages of novel technologies; (3) creation of new algorithms, standard operating procedures, data flow schemes and advanced statistical and computational methods that will directly facilitate analysis of the vast and complex data generated by genomics and imaging methods, to implement these new molecular pathology approaches in the clinic. We will focus on areas of clinical need where we believe genome-based assays will most rapidly enter the clinic, particularly the genetic diagnosis of acutely ill children and babies, genetic diagnosis in fetuses with congenital malformations, inherited subtypes of common diseases in adults, and the diagnosis and monitoring of patients with cancer through development of "liquid biopsies" from cell-free DNA in circulating blood.

A significant part of the proposed work will be done by practicing clinicians and diagnosticians in the framework of a purpose-designed Masters Research Programme in Molecular Pathology, to which experts in many fields will contribute, including those in the UK National External Quality Assurance Scheme (UK NEQAS) for Molecular Genetics and Pathology, which is based at the Royal Infirmary in Edinburgh. Together with our world-leading partners from the biotechnology and pharmaceutical industry, we will develop and integrate these genome and imaging-based methods to implement new diagnostic methods in healthcare and to produce and sustain a generation of "genomically-skilled" pathologists who will be leaders in the introduction of these methods into routine practice for the next generation of doctors and scientists.

Technical Summary

The Edinburgh-St Andrews Molecular Pathology Node will integrate proven strengths in molecular pathology, (training, development and clinical implementation), image analysis of complex phenotypes, informatics and genomics to build expertise, quality assurance and capacity in 21st century molecular diagnostics. Drawing on additional strengths in the MRC Human Genetics Unit, MRC Farr Institute, CRUK Cancer Centre, EPSRC-funded supercomputer facilities and industrial collaborations, we will establish a Masters by Research in Molecular Pathology, and thus train a new generation of scientists who will develop new assays, algorithms and standards for genome and epigenome analysis and interpretation for clinical use. We will implement state-of-the-art genome technologies to mainstream molecular diagnosis of Mendelian diseases in adult medicine and establish rapid genetic diagnosis of acutely ill children and neonates. We will develop "liquid biopsies" for managing cancer via genetic and epigenetic analyses of tumours and cell-free circulating DNA and will use state-of-the art digital imaging, image analysis and spectroscopy of tumours to provide more precise diagnoses and predictive stratification for patient management. The leads for this proposal all work at the interface of academia and the NHS and, by defining diagnostic standards in collaboration with the UK National External Quality Assurance Scheme (UK NEQAS) for Molecular Pathology and Genetics, hosted in Edinburgh by NHS Lothian, can ensure that these innovations are translated rapidly to clinical practice in the NHS. The Node's activities will be dovetailed with industry at every stage: technology development, assay design and implementation, data interpretation and clinical validation. The new Molecular Pathology Masters programme will produce and sustain a generation of new academic pathologists and help create a virtual Centre for Molecular Pathology as a basis for a substantive MRC Centre in the longer term.

Planned Impact

Through the clinical, academic and public engagement activities of the PI and co-Investigators, there has already been significant public, industrial and healthcare interest in the proposed activities of this Node.

Following the "Clinical Genomes Scotland" meeting in Edinburgh in October 2014, organised by Aitman, Porteous and Hastie, the Clinical Genetics Forum of Scotland held a number of meetings, culminating in the recommendation to the Scottish Chief Medical Officer (CMO) for the funding of 750 clinical genome sequences per year. Detailed discussions with the CMO have now led to provision for £1 million for clinical sequencing of Scottish genomes. This funding is part of an overall package of £10 million, to be jointly provided by the MRC and Scottish government, contingent on successful peer review of a single Scottish application for this funding (submitted February 2015, Aitman co-PI). If awarded, this funding will have a major impact on genome activities in Scotland and across the UK.

The public sector has also shown considerable interest in the genome and pathology activities of this grouping of researchers. For example, the PI has been invited by Genetic Alliance and Rare Diseases UK to speak at their annual reception at the Scottish Parliament in February 2015. Public events are planned by co-I Morris as part of the public engagement activities of the Scottish Farr Institute.

The proposed Node has also received considerable interest from local, national and international industry. The globally leading genome sequence company, Illumina, is one of our formal partners and will share early access protocols and software and has allocated a half-time postdoctoral scientist to work with us in their development labs. The leading multinational pharmaceutical company, Biogen Idec, has sponsored three Masters studentships and indicated its keenness to collaborate with us on genome-based disease stratification projects. Other companies, including Nucana, Definns, Qunitiles and Aridhia have indicated they will collaborate with the Node, once established, on clinical trials of genome-based assays.

Overall, the training of 18 Pathologists as Masters students on our MSc by Research, who will be versed in the most up-to-date genome and computational technologies in their applications to healthcare, will create a step-change in training of academic pathologists. We anticipate that some of our graduates will be the leaders in development of molecular diagnostics for the next generation of clinicians and healthcare scientists.

Publications

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Black HA (2016) De novo mutations in autosomal recessive congenital malformations. in Genetics in medicine : official journal of the American College of Medical Genetics

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Challis BG (2016) Familial Adrenocortical Carcinoma in Association With Lynch Syndrome. in The Journal of clinical endocrinology and metabolism

 
Description Edinburgh visit of Illumina CEO, CFO and CTO to Edinburgh Genomics facilities and SGP
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Informing the Future of Medical Genomics in Scotland, Precision Medicine Summit
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact Contributions to BEIS report on Precision Medicine and consideration by Scottish Government.
 
Description Member, European Research Council Advanced Grant Panel LS2
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
Impact Award of European Research Council Advanced grants.
 
Description Priorities for Translational Research and Innovation in Scotland, Scottish Policy Conferences, Cancer Care
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact Raising the profile of genomic research to the attention of the Scottish Government.
 
Description Scottish Clinical Genetics Research Day
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact Enhancement of Scottish clinical genetics research and knowledge and understanding of genomic tools available.
 
Description Scottish Genomes Partnership - Scottish Science Advisory Council
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact Working with the Scottish Science Advisory Council, raising the profile of Genomic Medicine and the potential for its future use to the Scottish Government via the publication of the report "Informing the Future of Genomic in Scotland"
 
Description Scottish Parliament Inquiry into Genomics in Healthcare for Scotland - Scottish Scientific Advisory Council
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact New funding proposal under consideration. Scottish Genomes Catalyst Fund, £3.5M, under auspices of Scottish Enterprise, now under review.
 
Description The Ethics of Genomic medicine, Royal Medical Society
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact Raising the profile of ethical issues surrounding genomic research amongst medical communities.
 
Description Visit of Cabinet Secretary for Health and Sport to Edinburgh Genomics
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact Raising the context of Scottish genomics to the attention of the Scottish Government.
 
Description Visit of Scottish Cabinet Secretary for Health and Sport to Scottish Genomes Partnership and subsequent policy dialogue
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact Proposal now under consideration by Scottish Government for future funding of genomics in healthcare.
 
Description Written and oral evidence to House of Commons Science and Technology Committee inquiry into Genomics and Genome Editing
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
Impact Gave UK-wide context to genomic medicine, particularly the participation of the devolved administrations and the interactions between Scottish and English national genome projects. Increased awareness of the SGP award and its impact in the Westminster and Scottish Parliaments.
URL https://www.parliament.uk/business/committees/committees-a-z/commons-select/science-and-technology-c...
 
Description Early Detection Committee - Project Award
Amount £483,949 (GBP)
Funding ID C22524/A26254 
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2018 
End 11/2021
 
Description Scottish Enterprise High Growth Spinout Programme
Amount £392,413 (GBP)
Funding ID PS7305CA54 
Organisation Scottish Enterprise 
Sector Public
Country United Kingdom
Start 02/2018 
End 01/2019
 
Description AstraZeneca Annual Genomics Partners Workshop 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution I made proposals for collaborative research with AstraZeneca.
Collaborator Contribution I sit on the AstraZeneca genomics advisory board.
Impact No impact yet
Start Year 2018
 
Description Cell-Free DNA Opportunities for Cancer Diagnostics 
Organisation Cancer Research UK
Department Edinburgh Cancer Research UK Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution We are developing strategies for analysis of cfDNA for early detection and diagnosis of cancer,
Collaborator Contribution We carry out in silico and wet lab investigation of cfDNA across several cancer types, in collaboration with oncologists and cancer surgeons in the Scottish NHS.
Impact No impact yet.
Start Year 2018
 
Description Genetic Studies of Motor Neurone Disease - SGP SAB 
Organisation Scottish Genome Partnership
Country United Kingdom 
Sector Learned Society 
PI Contribution We sequenced the genomes of 380 patients with motor neurone disease.
Collaborator Contribution We analysed the genome sequences and compared to controls. The data are part of an emerging collaboration with the New York Genome Center to identify disease genes for motor neurone disease.
Impact No impact yet
Start Year 2016
 
Description Genomics England partnership for sequencing patients in the Scottish NHS 
Organisation Genomics England
Country United Kingdom 
Sector Public 
PI Contribution Collaboration agreement signed, secure data transfer in place, genome sequence data being analysed collaboratively.
Collaborator Contribution Recruitment and sequencing of 1000 genomes of patients and their families in the Scottish NHS
Impact Written and oral evidence to House of Commons S&T Committee Inquiry in Genomics and Genome Editing
Start Year 2016
 
Description Liquid Biopsy and Early Detection, CRUK Brain Cancer Centre of Excellence Workshop 
Organisation Cancer Research UK
Department Edinburgh Cancer Research UK Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution We are developing strategies for analysis of cfDNA for early detection and diagnosis of cancer.
Collaborator Contribution We carry out in silico and wet lab investigation of cfDNA across several cancer types, in collaboration with oncologists and cancer surgeons in the Scottish NHS.
Impact No impact yet
Start Year 2018
 
Description Training collaboration with Scottish NHS 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution This award, in collaboration with NHS Lothian and NHS Tayside, have established a new Postgraduate Certificate in Molecular Pathology and Genomic Medicine at the University of Edinburgh. This is training clinicians and clinical scientists in new molecular methods in diagnostics and pathology that are relevant to state-of-the-art healthcare in the 21st century.
Collaborator Contribution I am PI on the award and have overseen the case to University of Edinburgh for establishing the course, have recruited teaching fellows, and assisted in design and content of the courses, as well as lecturing on several components of the course.
Impact 14 students from across South East Scotland, all NHS employees, have enrolled and all passed their first course. Student feedback is excellent. 11 medical trainees have enrolled on the related MMedSci Masters by Research. Of the 7 who have graduated to date, 6 have graduated with Distinction.
Start Year 2017
 
Company Name BIOCAPTIVA LIMITED 
Description BioCaptiva produce a medical device designed for extra-corporeal DNA capture from the blood by means of apheresis. Using the device cell-free DNA in the blood can be bound to a specifically designed polymer fixed to a matrix in an apheresis system. This allows for isolation of cell-free DNA in quantities unavailable via a traditional blood-draw, allowing for the detection of circulating-tumour DNA. 
Year Established 2018 
Impact No notable impacts to date.
 
Description Advanced Medicine: Introduction to Genomics, Advanced Medicine Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This was a lecture at the Royal College of Physicians Advanced Medicine symposium, attended by over 200 trainees policymakers and others.
Year(s) Of Engagement Activity 2018
 
Description Edinburgh Medical Debate - proposed motion 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact The subject matter of the debate was: "Edinburgh Medical Debate. Genome Screening: A Pandora's Box?". The motion for the debate was: "This house believes that the UK population should have whole genome screening." As proposer of the motion, we had pre-debate support for 36% of the audience, and post-debate support of 47%. A swing of 11% in favour of the motion!
Year(s) Of Engagement Activity 2017
URL https://media.ed.ac.uk/media/Edinburgh+Medical+Debate.+Genome+ScreeningA+A+Pandora%27s+BoxF/1_6nqurm...
 
Description Genomic Medicine: Yesterday, Today and Tomorrow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This was a lecture at the joint meeting of Genomics England and Brisith Society for Genetic Medicine, attended by over 200 clinicians, trainees and others.
Year(s) Of Engagement Activity 2018
 
Description Invited presentation to Royal College of Physicians of Edinburgh: "Genomic Medicine in Scotland: Progress, Prospects and Promises" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation to RCPE Senior Fellows - to inform and influence.
Year(s) Of Engagement Activity 2017
 
Description MRC Molecular Pathology Node Directors Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Lecture to Molecular Pathology Programme Directors and to MRC funders
Year(s) Of Engagement Activity 2018
 
Description New perspectives, new opportunities in life science and healthcare, BioDundee 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This was a lecture at the Biodundee healthcare research symposium, attended by over 100 trainees policymakers and others.
Year(s) Of Engagement Activity 2018
 
Description Opening presentation at Royal College of Physicians, Advanced Medicine Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited presentation on impact of advances in genomics on clinical practice.
Year(s) Of Engagement Activity 2018
URL https://www.rcplondon.ac.uk/events/advanced-medicine-2
 
Description Opening presentation, British Society for Genetic Medicine, Royal College of Physicians of London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited presentation on the Scottish Genomes Partnership and Scottish collaboration with Genomics England
Year(s) Of Engagement Activity 2017
URL http://www.bsgm.org.uk/bsgm-annual-meeting-2017/
 
Description Presentation at Scottish Parliament - Rare Disease Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Prof Zosia Miedzybrodzska, Lead Clinical Geneticist on this award, and for Scotland, gave an invited presentation on the Scottish Genomes Partnership and genome sequencing therein. Over 150 people from patient organisations, the public, and members of the Scottish Parliament including the Minister for Mental Health and the Chair of the Cross-Party Group on Rare Diseases were present.
Year(s) Of Engagement Activity 2018
URL https://www.scottishgenomespartnership.org