Category: Genomics England

Leading genomics expert awarded knighthood in the Queen’s birthday honours

Professor Mark Caulfield, the interim Chief Executive at Genomics England and Professor of Clinical Pharmacology at Queen Mary University of London, has been awarded a knighthood in the Queen’s Birthday Honours List.

Since 2013 Professor Caulfield has been instrumental in delivering the world-leading 100,000 Genomes Project, which hit its target of sequencing 100,000 whole genomes in 2018 and has already delivered life-changing results for patients.

This NHS transformation programme used whole genome sequencing to bring new diagnoses to people with rare diseases and to help choose cancer therapies.

To increase the value for participants in the project, Professor Caulfield established a coalition of 3,000 researchers worldwide and assisted the NHS in the creation of the National Genomic Test Directory. This will offer equitable access for 55 million people, depending on clinical need, to the appropriate genomic tests via a new National Genomic Medicine Service.

Professor Mark Caulfield said:

I have been incredibly lucky to stand amongst and alongside giants from our NHS, Genomics England, our universities, the government, our funders and most importantly, our participants. Together they helped me to transform genomics in healthcare. Their commitment, generosity, and trust has made our nation the world leader in the application of genomic medicine in the NHS. I am deeply honoured and thank every one of those who made this possible.

Jonathan Symonds CBE, the Chair of Genomics England said:

Mark’s knighthood is a fitting recognition of his pioneering and tireless work in genomics. He is an extraordinary clinician scientist whose contribution and leadership are respected worldwide for delivering the 100,000 Genomes Project. His role as Chief Scientist of Genomics England has seen whole genome sequencing reveal new diagnoses, improve treatments, and fuel medical research. It has benefited and will benefit many, many people across the world. This award is richly deserved.

Professor Colin Bailey, President and Principal of Queen Mary University of London, said:

I am delighted that Mark’s outstanding work in genomics has been recognised with such a prestigious honour. His pioneering work will pave the way for new diagnoses and precision healthcare across the globe. He is truly one of our stars at Queen Mary, and it is wonderful to see his contribution to science and medicine recognised with this honour.

Professor Caulfield graduated in Medicine from the London Hospital Medical College in 1984 and trained in Clinical Pharmacology at the Medical College of St Bartholomew’s Hospital and Queen Mary University of London, where he holds a Chair.

He has made substantial contributions to the discovery of genes related to cardiovascular health, cancer and rare diseases, including the discovery of more than 1,000 gene regions for blood pressure. He is amongst the top 1 per cent of the most highly cited researchers worldwide and his clinical pharmacology research has changed national and international guidance for high blood pressure.

Since 2000 he has been a Fellow of the Royal College of Physicians, and in 2002 he was appointed Director of the William Harvey Research Institute at Queen Mary University of London.

In 2008 he was elected a Fellow of the Academy of Medical Sciences, and became Director of the NIHR Barts Biomedical Research Centre.

Professor Caulfield was the academic lead for the creation of the Barts Heart Centre, bringing three hospitals together in 2015 to create the UK’s largest heart centre.

In 2013 he became an NIHR Senior Investigator and was appointed Chief Scientist for Genomics England where he has led the scientific strategy and delivery of the 100,000 Genomes Project, which sequenced the 100,000th genome on 5 December 2018. He became interim Chief Executive of Genomics England in January 2019.

The funders of this healthcare transformation leading to this award:

The 100,000 Genomes Project was primarily funded by the National Institute for Health Research (which also helped to recruit participants and store biological samples). Generous funding also came from the Wellcome Trust, the Medical Research Council, Cancer Research UK, the Department of Health and Social Care, NHS England, and the administrations of Scotland, Northern Ireland and Wales.

Matching mitochondria – Important new research uses 100,000 Genomes Project data

Professor Patrick Chinnery, Dr Ernest Turro, and Dr Wei Wei

Scientists publish new research using data from the 100,000 Genomes Project rare disease programme

Scientists from the University of Cambridge have announced a discovery about the inheritance of mitochondrial DNA using data from the 100,000 Genomes Project. The scientists are part of the neurology domain of the Genomics England Clinical Interpretation Partnership (GeCIP). These important scientific findings represent the beginning of a stream of valuable discoveries that will come from the 100,000 Genomes Project data.

The research has been published in the journal, Science. We asked study authors Professor Patrick Chinnery, Dr Ernest Turro, and Dr Wei Wei about their research. 


What do we mean by ‘mitochondrial DNA’?

Mitochondria, the ‘powerhouses’ inside cells that produce energy, have their own DNA called mitochondrial DNA. This is distinct from so-called ‘nuclear DNA’, which is contained in the cell’s nucleus and determines most of a person’s characteristics. Our nuclear DNA comes from both our mother and father, but our mitochondrial DNA only comes from our mother. Each cell can contain hundreds of mitochondria.

Nuclear DNA and mitochondrial DNA can change – these changes are called mutations. However, not all of the hundreds of mitochondria in a cell will have the same mutations. Having a mixture of normal and mutated mitochondrial DNA is called ‘heteroplasmy’.

Where did the data used in this study come from?

Our study was based on the analysis of nuclear and mitochondrial DNA in whole genome sequences from 53,300 individuals who were part of the National Institute for Health Research BioResource – Rare Diseases project, and the rare diseases programme of the 100,000 Genomes Project.

What did your study find?

In our study, we investigated how mitochondrial DNA mutations and heteroplasmies change when they are passed from a mother to her child. We found that 45% of people carry at least one mutation that affects more than 1% of their mitochondrial DNA. The proportion of mitochondrial DNA that carries a particular mutation can change when mitochondria are passed from mother to child. For some, the percentage level of heteroplasmy increases, and for others it decreases. This shapes mitochondrial DNA in the human population.

We also found that, for approximately 1 in 40 people in our UK-based study, their mitochondrial DNA originates from a different geographical population than their nuclear DNA. In these individuals, new mutations in their mitochondrial DNA are more likely to match the geographic origins of the nuclear DNA than the geographic origins of the mitochondrial DNA. This suggests that the nucleus is ‘shaping’ our mitochondrial DNA when it is passed from mother to child.

Do these findings have implications for patients or the public?

Although there are no immediate implications for patients or the public, our work gives the first clue that our cell nucleus ‘prefers’ some kinds of mitochondrial DNA. This might be important when carrying our ‘mitochondrial transfer’ to help prevent the inheritance of severe mitochondrial diseases.

Mitochondrial transfer is an in vitro fertilisation (IVF) technique for preventing inherited mitochondrial diseases. It involves taking the DNA out of a woman’s egg or embryo that has faulty mitochondria and transferring it to a donor egg or embryo with healthy mitochondria.

Matching both the mitochondrial background and the nuclear background of the donor could be important when selecting potential mitochondrial donors, although further work is needed to show whether this will be important in the long term.

Dr Freya Boardman-Pretty from the Genomics England Clinical Interpretation Partnership (GeCIP) team, explains how the GeCIP helps to enable important research like this to happen.

How does being involved with the GeCIP help scientists to carry out important research?

The GeCIP (Genomics England Clinical Interpretation Partnership) is a community of researchers and clinicians from academia and healthcare, who are based in the UK and worldwide. This community uses the 100,000 Genomes Project data to improve our understanding of genomics and health.

The Project dataset is an incredibly rich and unique resource. As well as the 100,000 whole genomes from participants, it also includes detailed clinical data such as linked longitudinal health records from the NHS. Access to this detailed and comprehensive information helps scientists and clinicians to answer questions about health that we have not been able to answer before.

How does the work of the GeCIP community help patients?

One important aim of the GeCIP is to use the community’s expertise to find diagnoses for the 100,000 Genomes Project participants where our interpretation pipeline has not found a possible cause of their disease. This means Genomics England can feedback additional diagnoses to individual patients and improve the way results are interpreted in the future.

GeCIP includes many diverse research areas, called “domains”. Scientists studying rare diseases often look for novel genes that might play a part in how a disease develops and progresses. Cancer researchers aim to identify new mutations that might promote the development of cancer, or use genetic and clinical data to study how cancers change when patients undergo treatments.

Identifying relevant genes in disease can open up new avenues of research, and help us to find new treatment options for patients.

The Science Advisory Committee and Access Review Committee assess each domain’s research aims before they begin their work. This also allows participants to review which questions and problems scientists are working on.

What does being a member of the GeCIP involve?

Members of the GeCIP apply to join wanting to answer specific questions, but we also expect them to contribute to wider knowledge across the Project, such as adding expert reviews to PanelApp or helping to train new GeCIP members.

One of the main principles of the GeCIP is that research should be collaborative rather than competitive. Ongoing research is registered so that other GeCIP members can find projects that they might like to work on with other scientists. Hopefully, this avoids duplicating research efforts and ultimately leads to better scientific results.

The GeCIP is constantly growing, with numerous applications to join every week. Individuals can apply to join here.

You can read more about this study on the University of Cambridge website

Genomic medicine will change the relationship between the NHS and the people who use it, according to a major new public dialogue project

The more widespread use of genomic medicine – applying knowledge about a person’s genetic information to guide and improve their healthcare – will change the relationship between the UK public and the NHS, according to a new report launched today. ‘A public dialogue on genomic medicine: time for a new social contract?’ explored public aspirations, concerns, and expectations about the development of genomic medicine in the UK. It was commissioned by Genomics England and co-funded by UK Research and Innovation’s Sciencewise programme in support of public dialogue on scientific and technological issues.

Led by Ipsos MORI’s Public Dialogue Centre, in-depth discussions between experts and members of the public across the country revealed widespread optimism about the potential of genomic medicine to improve our health and develop new and better treatments for disease and ill health. However, the report found that the delivery of genomic medicine will need widespread support and engagement from the public, clinicians, and researchers alike.

The dialogue reported that advances in genomic medicine may change public expectations around donating their data; and that clinicians and researchers will need to be equipped with ‘genomic literacy’ to support patients and donors and explain the ever-closer relationship between research and clinical care. The ways that medical charities, research organisations, and industry work with the NHS, and the importance of basic biological research, will also need to be better explained.

The NHS was founded on a common set of principles and values, as outlined in the NHS Constitution, that bind together patients, the public and NHS staff, helping the service work in an effective and equitable way. The new dialogue revealed that although participants were unfamiliar with the terminology around this ‘social contract’, they had very clear perceptions of how the NHS works and the ‘deal’ between the service and patients.

The report recommends that these advances from genomic medicine– particularly where they affect the core values of reciprocity, altruism, and solidarity (see notes below) – should be enshrined in the NHS Constitution.

The project also found that whilst there was widespread enthusiasm and support for genomic medicine, the public also have clear limits for how far they thought genomic data, and information derived from it, should be used. These red lines included genetic engineering, use of genomic data to differentiate groups within society, and for predictive insurance tests and targeted marketing. Participants wanted assurances that there is a robust governance framework and consent process in place that makes it clear what the intended use of their data is.

The Chief Medical Officer for England, Professor Dame Sally Davies, said: “I am delighted to see the publication of this important and timely report. It is increasingly clear that developments in genomics have the potential to significantly improve human health. Furthermore, the ability to provide the best care for patients can be greatly enhanced by comparing their data with that of many others. These benefits, which depend upon the safe collection, secure storage, and controlled use of patient information, are only fully achievable and sustainable in the context of well-founded public trust and confidence.”

Professor Michael Parker, Wellcome Centre for Ethics and Humanities, University of Oxford, said: “This report highlights the crucial role that ethics and participant engagement play in establishing and maintaining public trust in genomics. It is essential reading for everyone with an interest in genomic and data-driven medicine. It presents the results of an inclusive and thorough process of public dialogue and makes a vital contribution to ongoing discussions about genomic medicine. It reveals that the relationship between the NHS, patients, and the public is currently understood in terms of three core values: reciprocity, altruism, and solidarity. These values are likely to continue to inform the understanding of the appropriate relationship between medicine, research, and society as genomic medicine plays a more central role in healthcare.”

Professor Mark Caulfield, Chief Executive of Genomics England, said: “This dialogue is enormously important and timely as genomic medicine becomes mainstreamed in healthcare.  We need to support healthcare professionals as they work with patients to discuss the risks, benefits and other implications of genomic medicine with patients and the public. We need to describe clearly how genomic data will create a feedback loop that benefits both research and clinical care.  Building trust in this exciting and revolutionary area of medical science is absolutely essential to its success. Involving participants in all stages of our pioneering 100,000 Genomes Project was instrumental in putting a trusted system in place.”

Sarah Castell, Head of Futures at Ipsos MORI and the dialogue lead, said: “The members of the public at our events put a lot of work into this dialogue as they uncovered the ethical and practical dilemmas which the growth of genomics might bring. They questioned experts, explored case studies and examples, and developed their own views with great insight and flexibility of thought.  By the end of the sessions, participants expressed the same requirements from genomics as the public often asks of new technologies: they want genomics to bring clear benefits, to avoid unintended negative social consequences, and for those benefits to be shared fairly across all of society.”

Simon Burall, Programme Director for Sciencewise, said “Sciencewise has supported over 50 public dialogues on a wide range of scientific innovations. This project with Genomics England demonstrates why government departments invest in deliberative dialogue. By bringing together a diverse and inclusive sample of the public to engage deeply with the issues raised by the latest scientific advances, policy makers can get beyond the loud voices in the debate to gain insight into public perspectives. This helps them to understand how the public balances the trade-offs between the benefits that many of these innovations bring, and the societal harms that may also result, leading to better policy and a more trustworthy system of governance for the technology in question.”

Health Minister Nicola Blackwood said: “Genomic medicine has enormous potential to transform healthcare by diagnosing diseases earlier, personalising care to individual patients, and giving researchers the crucial information they need to develop cutting-edge treatments of the future. We are determined to embrace it through our Long Term Plan for the NHS. It is absolutely vital people have the confidence that their data will always be protected to the highest standards – and the Government has introduced tough new legislation to make this happen.”

 Download the report (PDF) here.


The participants in the dialogue had very clear perceptions of why the NHS works. These were based on 3 concepts:

  • Reciprocity – the NHS will provide the best available care, in return for the public valuing that care
  • Altruism – the public want healthcare and research to benefit others as well as themselves
  • Solidarity – everyone pays their fair share and contributes individually to reducing the public health burden


  • Ninety-seven members of the public, and thirty experts came to evening and reconvened day-long Saturday events, held in Coventry, Edinburgh, Leeds, and London.
  • A proportion of each group in each location was reconvened to a final Genomics summit event in London (n=23 in total), where the group was again joined by experts.
  • A total of forty-three experts attended the dialogue workshops and the Genomics summit.
  • A rapid light-touch literature review was conducted to inform the dialogue materials and to ensure that the project built on the work of previous social research on attitudes to genomics.   A stakeholder workshop including 19 participants also helped shape the framing of the dialogue, the materials and examples given to workshop participants.

The dialogue method involves in-depth discussion with relatively small groups of people; participant views are therefore not representative of the views of the wider public in the same way as a large scale survey. Nevertheless, the depth of discussion, time for reflection, scope of information provided, and interaction with experts, means that the views expressed here can be taken as a good indication of how an informed public might respond to complex ethical and practical questions around genomics.

Qatar Genome Programme and Genomics England formalise collaboration

Genomics England has signed a Memorandum of Understanding (MoU) with Qatar Genome Programme. The agreement lays the foundation for Qatar and the UK to develop a collaboration focusing on areas of research in genomics with global impact. The strategic research and development agreement aims to enable novel scientific discovery, and provide medical insights in genomics and precision medicine.

“This partnership aims to foster our shared goals for advancement of precision medicine and to facilitate common genomic research initiatives,” said Dr Richard O’Kennedy, Vice President for Research, Development, and Innovation at Qatar Foundation.

“Together we can push the boundaries further towards a new era of medical practice, where genomics can play a central role.”

Professor Mark Caulfield, Interim Chief Executive and Chief Scientist of Genomics England, said: “Genomics is a global, multi-stakeholder endeavour transforming healthcare. This collaboration will help expand the legacy of the 100,000 Genomes Project beyond the UK, and will allow us to better serve the diverse population of the UK. We are excited to share our expertise, and equally excited to learn from the approach of the Qatar Genome Programme.”

The MoU outlines a number of research activities between Qatar Genome Programme and Genomics England, such as establishing common frameworks to standardise genomic strategies for healthcare implementation; the evaluation of new technologies for whole genome sequencing; the cross-analysis of both national datasets; and the exchange of expertise related to educational programs. The two organisations will work together to share ideas, policies and regulations, technical expertise, and bioinformatics tools, and also to exchange staff, data and expertise in the field of genomics.

Commenting on the importance of the agreement, Professor Asmaa Al Thani, Board Vice-Chairperson of Qatar Biobank and Chairperson of the Qatar Genome Programme, said: “This agreement will see our two projects benefiting from a strategic alliance and the pooling of research talent and resources from both nations. The programme will also hopefully generate key industrial partnership opportunities enabling vital medical insights and breakthroughs.”

Attending the signing ceremony, His Excellency Mr Ajay Sharma, Her Majesty’s Ambassador to the State of Qatar, said: “I am delighted that the Qatar Genome Programme and Genomics England are signing this Memorandum of Understanding. The partnership between these leading institutions in genomic research will, I am sure, make an important contribution to tackling the healthcare challenges of today and tomorrow.

“This is another example of how the UK and Qatar are working together on Qatar National Vision 2030; and how this collaboration is of benefit to both our countries and others.”

Industry collaboration already benefiting participants of 100,000 Genomes Project

Alexion and BioMarin, both members of Genomics England’s Discovery Forum, have identified previously undiagnosed patients with life-threatening kidney and neurological diseases.

Diagnosing children likely to develop kidney failure

Nephronophthisis (NPHP) is a childhood genetic disorder primarily affecting the kidneys. It is rare (around 1 in 60,000 births) and usually results in kidney failure by the age of 15.  It is responsible for 15% of cases of childhood end-stage renal failure – with no preventative treatments currently available.

Using Genomics England’s dataset, global biopharmaceutical company, Alexion, has identified 14 undiagnosed patients, recruited as part of the 100,000 Genomes Project’s rare disease programme, who carry the gene deletion causing the disease. These findings have been shared with Genomics England and fed back to the patients’ NHS clinical teams.

“NPHP is a severe and devastating disease with significant unmet medical need. Our work with Genomics England has enabled us to identify previously undiagnosed NPHP patients, and it has helped us to understand the wide clinical spectrum that these patients show,” said Dr Guillermo Del Angel, Senior Director, Data Science, Genomics, and Bioinformatics at Alexion.

This discovery is an exciting first step in a broader collaboration between Alexion and Genomics England in applying data sciences and artificial intelligence across a spectrum of genomic and clinical data. The aim is to accelerate the diagnosis of patients suffering from rare diseases, enable paths of intervention, and bring hope to those with the disease and their families.

New hope for Batten Disease

Neuronal ceroid lipofuscinoses 2 (CLN2) is a very rare, inherited disorder caused by mutations in the TPP1 gene, and is one of a group of life-limiting conditions collectively known as Batten Disease. The symptoms typically emerge in children between the ages of two and four. CLN2 can lead to seizures, muscle twitches, vision loss, intellectual disability, and behavioural problems. Around 30-50 children live with the condition in the UK, and life expectancy is around 10 years. Currently, there is no cure or life-extending treatment for CLN2.

Biopharmaceutical company BioMarin, is another Discovery Forum member focused on rare disease patients.  It has identified one patient recruited into the 100,000 Genomes Project for a condition unrelated to CLN2, but who carries two pathogenic mutations of the TPP1 gene. This new information has also been fed back to the patient’s NHS clinical team.

BioMarin intends to engage the UK’s National Institute for Health and Care Excellence (NICE) and NHS England on the use of its cerliponase alfa treatment for patients with CLN2 in England. Ultimately, it is hoped that the work from BioMarin and others, supported by evidence from the Genomics England database, will bring clinicians more treatment options for patients with CLN2.

“The focus of rare undiagnosed diseases in Genomics England’s 100,000 Genomes Project provides us with a unique opportunity to better understand the clinical spectrum of devastating childhood diseases, and to develop targeted therapeutics that can impact patients and their families.  We are excited about these initial findings and about improving alignment between disease diagnosis and access to available therapeutics in the UK and around the world,” said Dr Lon Cardon, Chief Scientific Officer at BioMarin.


These two examples highlight the range of value that Genomics England’s Discovery Forum is providing to multiple stakeholders. Access to the data is allowing drug developers to strengthen the body of clinical insights for target cohorts; in turn their work is immediately fed back into clinical reporting that Genomics England provides for Project participants through the NHS.

This work exemplifies the Discovery Forum aim to improve patient outcomes. It is a goal that relies on a variety of stakeholders working together and sharing knowledge. While the dataset is a valuable research asset, it is the researchers themselves who will define its value.

Joanne Hackett, Chief Commercial Officer, Genomics England, said: “The 100,000 Genomes Project has succeeded in its role as a pilot project for establishing a genomic medicine service through the NHS. Our ambition is to grow the legacy of the Project to improve patient outcomes across the globe. Through the Project, and in collaboration with our clinical delivery partners across the NHS, we have built an extraordinarily rich dataset that will continue to grow in breadth and depth.

“The potential applications of this are exciting. There are clear immediate benefits in developing new diagnostics technologies and data analysis tools. There are also long-term benefits that tie in with the paradigm shifts we are seeing in the pharmaceutical industry. We are leaving the age of the block-buster drug. The focus has moved to targeted therapies, drug repositioning, and reducing the failure rate of clinical trials. It is here that we see a lot of exciting potential applications of the 100,000 Genomics Project cohort data.”

Chair of the Genomics England Participant Panel, Jillian Hastings-Ward, said: “People signed up for the 100,000 Genomes Project in the hope that their data could be useful in advancing scientific discovery as well as, perhaps, helping them individually. This news demonstrates that the Project is starting to make tangible progress on both of these fronts.”

Find out more about how we work with industry.

Genomics England and industry partners complete first phase of liquid biopsy study

Genomics England has announced the successful completion of the first phase of its collaboration with Inivata and Thermo Fisher Scientific to investigate the use of liquid biopsies in cancer. This is part of a pilot project aiming to:

  • assess the suitability of circulating tumour DNA (ctDNA) samples collected by the NHS during the 100,000 Genomes Project
  • perform objective technology evaluation of the various market offerings in liquid biopsy
  • generate evidence for the potential consideration of such technology implementation in future routine healthcare for better disease treatment or prevention

Inivata and Thermo Fisher Scientific analysed around 200 blood plasma samples, donated by participants of the 100,000 Genomes Project, for their suitability for Next Generation Sequencing-based testing. The analysis also served to further establish the capacity of Inivata’s liquid biopsy platform, InVision®, and Thermo Fisher Scientific’s Oncomine™ Pan-Cancer Cell-Free Assay to identify the presence of cancer.

The results of the study showed that the plasma samples collected were of a high quality and produced reliable results when analysed. These results were consistent across all cancer types.

The collection methods were shown to allow for ctDNA analysis, opening up a range of possibilities for the further analysis of banked samples using liquid biopsy technology such as those provided by Inivata and Thermo Fisher Scientific. This demonstrates the strong potential for liquid biopsy to improve cancer management and outcomes for UK patients.

These results, and those from the two subsequent phases, will be shared with researchers in the UK and around the world providing additional multiomic data to members of the Genomics England Clinical Interpretation Partnership (GeCIP) and Discovery Forum.

The second phase of the study aims to generate data to form the basis of an objective technology assessment between pre-selected liquid biopsy companies. This will inform future procurement and research strategies to improve patient outcomes. The final phase will be a proof of concept longitudinal ctDNA sample study. This will help develop less invasive sample collection techniques, more effective monitoring processes, and ultimately better cancer care.

Clive Morris, Chief Executive Officer at Inivata, said: “We are delighted to be working with Genomics England, and to see the progress being made with this collaborative study. The successful end of this initial phase demonstrates the quality of the sample collection from all sites and will enable the exploration of a number of ways of providing further insights to patients. Inivata and Genomics England share a commitment to delivering innovations to UK patients, unlocking exciting new treatment options and improving patient care.”

Joydeep Goswami, President of Clinical Next Generation Sequencing and Oncology for Thermo Fisher Scientific, said: “The application of liquid biopsy to better understand cancer holds great promise as a less-invasive and potential early detection approach for the future of patient care. The successful completion of phase one of this program, enabled by the leadership and support from Jacqui Shaw’s lab at the University of Leicester, corroborates the potential of this approach. We look forward to the next steps in our ongoing collaboration with Genomics England.”

Mark Caulfield, Interim Chief Executive Officer at Genomics England, said: “Our priority at Genomics England is to improve patient outcomes. The potential that liquid biopsies represent for earlier diagnosis and tracking of cancer is well documented, but nonetheless remains very exciting. There is still much to do to establish clinical utility and suitability of the technology. As we continue to carry out this work, we keep in mind what this means for patients – significantly less invasive procedures, and the potential to detect cancers much earlier and treat them much more effectively.

Joanne Hackett, Chief Commercial Officer at Genomics England, said: “Exploring new and developing technologies is central to our mission at Genomics England. If we are to keep the UK a world leader in the delivery of genomic medicine, it is going to be through collaborations such as this with leading technology companies. The results of the first phase of our liquid biopsy trials are very encouraging, and we look forward to further rigorous testing through phase two.”

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Genomics England’s PanelApp software is now open source

The software behind Genomics England’s PanelApp, a crowdsourcing platform for sharing and evaluating gene panels, has now been made publicly available for the scientific and clinical community to use. Data from the 100,000 Genomes Project will not be shared or be made open source.

By making the PanelApp software open source, scientists in organisations across the world will be able to upload their own data to create gene panels for research.

PanelApp is a knowledgebase of virtual gene panels for rare diseases and cancer. It has a crowdsourcing tool that allows experts from around the world to provide reviews of genes and the underlying evidence for what may be causing disease. These panels are publicly available to browse, download, and query.

In each panel, genes are ranked using a traffic light system.  Using specially designed software tools, the Genomics England Curation Team assess the crowdsourced expert reviews and evidence from other sources to define which genes have a high level of evidence for causation in a disease. Gene panels with strong evidence are classified as “green” for genome interpretation. The gene panels are used in Genomics England’s 100,000 Genomes Project to help prioritise genetic variants to gain diagnoses for rare disease patients, or highlight important inherited variants in cancer susceptibility genes for cancer patients. PanelApp is also being used to help support the process of gaining a consensus on which genes should be included in tests for the NHS Genomic Medicine Service.

The PanelApp software, which includes the review and curation tools described above, has been released in GitHub, making it available for the bioinformatics, research and clinical community to utilise.

What now for 100,000 Genomes Project participants?

Participant Panel Chair Jillian Hastings Ward took the opportunity to grill Genomics England’s Chief Scientist and interim Chief Executive Professor Mark Caulfield on film while both were at the Festival of Genomics in January 2019. See some of the key answers below.

What are you going to do with the data sequenced through the 100,000 Genomes Project this year?

Our first priority is to get reports back to those who have not yet received a result. Our second priority is to revisit the genomes for people who haven’t yet got an answer, to see if new knowledge or new ways in which we can analyse a genome will be able to find answers.

So far the analysis has been focusing on individual gene panels as a starting point. Can you tell us about what will happen next?

When we first started, the knowledge base meant we had to focus on genes, so we developed panels using literature known worldwide. For some people – around 40% in intellectual disability – that is making a diagnosis and getting them answers quite quickly. But we are continually evolving those panels and now we’re looking outside the genes, in other parts of the genome, for variations that might cause disease, and we are bringing them as they are invented. That’s the virtue of having your whole genome – we can go back with new knowledge to get new answers for our participants.

What is the timeframe?

We are aiming to analyse everyone’s genome for the first time and returning results back to the NHS by July 2019. Then there will be a little bit of a delay while they look at those reports and consider whether it is reliable enough to give that information back to the participants, as these clinicians are the ones caring for those patients.

Watch the video with Professor Caulfield’s full answers below:

This video accompanies a letter sent from Professor Caulfield to all participants of the 100,000 Genomes Project.

Jonathan Symonds appointed new Chair of Genomics England

John Symonds (left) and Sir John Chisholm (right)

Jonathan Symonds CBE is to be appointed the new Chair of Genomics England. Following the success of the 100,000 Genomes Project, Genomics England announces that its Chair, Sir John Chisholm will step down on 29 January 2019. Sir John, who has led the company since its inception in 2013, indicated his decision to leave to the Board once Genomics England realised its 5 year ambition to sequence 100,000 whole genomes in early December.

Jonathan Symonds has more than 30 years’ experience across a spectrum of life science enterprises. As Senior Non-Executive Director on the Genomics England Board, he has been part of Genomics England since 2014 and increasingly engaged in the oversight of Genomics England’s forward plans.

The Chief Executive of Genomics England, Professor John Mattick is to leave the company following his successful work on crafting the recently announced UK genomics vision. Genomics England’s Chief Scientist, Professor Mark Caulfield has agreed to act as interim Chief Executive. The search for a permanent appointment will begin next week.

The incoming chair of Genomics England, Jonathan Symonds said:

“Sir John Chisholm’s accomplishment has been extraordinary. His skill and visionary leadership have enabled the UK to become the leader of global efforts to harness the potential of genomic science and healthcare and to realise the potential of personalised medicine. He has worked closely with partners across the NHS, academia, and industry to create an extraordinary infrastructure for genomic research and health.

“Professor John Mattick is a formidable scientist who has argued passionately that genomic medicine can transform medical research and healthcare and has helped us build an ambitious vision for the role genomics can play in the future of healthcare. We would like to thank John for the contribution he has made to Genomics England and we wish him well for the future.

“As we look to the next phase of Genomics England, in partnership with the NHS, to deliver genomics based diagnostics in clinical care, I’m delighted to announce that Professor Mark Caulfield, who as chief scientist directed much of the work of the 100,000 Genomes Project, will act as our interim CEO. Mark will head Genomics England as we rise to the challenge of speeding up diagnosis and personalised treatments through the NHS with the Genomic Medicine Service and keep the UK at the leading edge of genomic medicine and science.”

Jonathan Symonds added:

“I am delighted to accept the honour of becoming Genomics England’s Chair. Sir John’s shoes will be hard to fill.  We have an exciting challenge ahead in partnership with the NHS, as we continue our efforts to prevent disease, unlock new treatments, improve and accelerate diagnosis and to help patients receive the best care tailored to their needs.”

Sir John Chisholm said:

“I am so proud and pleased with the extraordinary achievement of realising our ambition of sequencing 100,000 whole genomes within the NHS. And this felt like the right time for me to move on. It was an unprecedented team effort involving thousands of researchers, clinicians and others across the NHS, academia, industry, and beyond. Most especially thanks to the generosity of more than 93,000 NHS patients and their family members who continue to put their faith in Genomics England as the work to push back the boundaries of genomic science and healthcare goes on.”

 The Secretary of State for Health and Social Care, Matt Hancock MP said:

 “We should all be incredibly excited about the potential for genomics to improve the lives of patients and transform healthcare – and I’m proud that the UK is leading the world in this area. Sir John Chisholm has been paramount in the success of the 100,000 Genomes Project and I want to thank him for his inspiration and hard work. I welcome Jonathan Symonds CBE to drive forward the next stage of British global leadership in genomics and look forward to working with him to deliver our commitment to sequence one million whole genomes over the next five years – helping improve peoples’ lives.”

Lord David Prior, the Chair of NHS England said:

“The delivery of the 100,000 genomes project within a working health system is an achievement which is viewed in awe all over the world. It was only possible due to the close partnership between Genomics England and NHS England. We have in Jonathan Symonds an enormously accomplished Chair to take over from Sir John Chisholm. I look forward to working with him and Professor Caulfield to tackle the delivery of even more benefit for patients, science and industry from the next 5 year vision. This is almost certainly the biggest breakthrough in clinical practice in my life time, it makes predictive and personalised medicine a reality.”

Professor John Mattick said:

“I am very sorry to be leaving Genomics England at this time. Genomics England has an exciting future through its partnership with NHS England to deliver personalised medicine, and fuel innovation and investment in genomic medicine. I am pleased with the contribution I was able to make in developing the vision for the next 5 years that the Secretary of State announced in October, and in laying out a plan to achieve this vision. I wish Professor Mark Caulfield and all the staff at Genomics England well with their future endeavours.”

The journey to 100,000 genomes

Genomic potential

Pinpointing the beginning of the 100,000 Genomes Project isn’t easy. It could be argued that Crick, Franklin and Watson started it all in 1953; or Frederick Sanger’s pioneering sequencing technologies in the late ‘70s; perhaps the Human Genome Project in 2003; or even the UK10K project in 2008. Our journey, however, began in 2012 with the announcement of the Project and, in 2013, the creation of Genomics England to drive it to completion.

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.

Building a genomic medicine infrastructure

The UK was brave enough to lead the way – announcing the groundbreaking 100,000 Genomes Project, which aimed to sequence 100,000 whole genomes from around 70,000 participants with rare disease, their families and people with some cancers. The decision was backed by robust government support – both political and financial – which included over £300 million of investment.

Building a genomic infrastructure – partnership on an industrial scale

As we celebrate the sequencing of the 100,000th whole genome just five years later, it is important to remember the scale of the achievement. For those of us here at the beginning, the prospect was simultaneously exciting and daunting. 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. With important objectives to create a consent-based and transparent programme that fostered an emerging UK genomics industry – our ultimate aim was to bring real and lasting change to NHS care.

The challenge, described by one colleague as “building the plane whilst flying it”, 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.

Genomics England began its close relationship with NHS England to recruit the first participants in 2014. In the same year, NHS England created 11 Genomic Medicine Centres (GMCs), eventually growing to 13 in 2015, and today joined by organisations in Northern Ireland, Scotland and Wales.

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. We cannot underestimate the commitment, skill and hard work of thousands of NHS staff who have pioneered these GMCs and the cause of genomic medicine in the NHS.

At the start of 2015, another piece of the infrastructure puzzle fell into place with the opening of the NIHR Biosample Centre to store samples from the Project. And just two months later, we established the Genomics England Clinical Interpretation Partnership (GeCIP). GeCiP brings together thousands of researchers and clinicians from across the world – granting them carefully controlled access to our database to power new discoveries in genomic medicine. Today GeCIP research covers 42 areas – known as ‘domains’ – including rare cardiovascular and neurological disorders, and cancers such as breast, lung and ovarian.

Early in the Project, we realised that 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. It has involved a huge commitment from our bioinformatics team and others – but has resulted in one of the world’s few semi-automatic bioinformatics pipelines.

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.

In 2015 we also began to explore how to align our work with the needs of industry – the companies that will eventually turn genomic discovery into routine treatments. This started with the GENE Consortium, which evolved in 2017 into the Genomics England Discovery Forum we see today. The Forum is a platform that allows us to bring together charities, patients, researchers, clinicians and others with industry partners to share perspectives and better understand how to speed discoveries from the laboratory bench to the patient’s bedside. In the past few months, the value of the Forum has been demonstrated with members discovering previously undiagnosed patients in our database – with the hope that this will lead to better diagnosis and the development of more effective treatments.

People powered healthcare

From the outset, the Project recognised that genomic medicine could not succeed without the understanding, trust, acceptance and consent of patients. Genomic medicine is truly “people-powered healthcare”. It heralds a changing relationship between the patient and the NHS, with a new consent model where healthcare and research become indivisible. It is important to understand that new technology and the use of data will only be socially and clinically enabled if it is trusted by the patient.

100,000 Genomes Project timeline

In 2016 Genomics England established the Participant Panel, which acts as an advisory body to our Board. The Panel is at the heart of our decision making processes, with members sitting on the Access Review Committee, the Ethics Advisory Committee and the GeCIP Board. Involving participants at this fundamental level ensures that the Project is always responsible to the people who drive it.

It also underlines the importance of the Project to participants. Participant Panel Deputy Chair, Rebecca Middleton, has said, “The Project brings me something new – hope. Whether in 5 or 15 years, new genomic discoveries may be able to help me.”

Ensuring that we are able to gain the trust of patients demands that we understand their attitudes to genomic medicine – and this inspired the ‘Genomics Conversation’ in 2016. The Conversation is a genuine engagement project – not seeking to influence its audiences, but rather to listen.

And what is it that patients get from the investment of their trust, understanding and consent?

Even at this early stage, genomic medicine is helping to transform cancer services – making real progress in providing DNA of sufficient quality for whole genome sequencing – an issue that has hampered efforts to apply genomics in cancer diagnosis and treatment around the world. NHS England is re-aligning its laboratory services as it moves from formalin-fixed paraffin embedded (FFPE) to Fresh Frozen (FF) sample handling.

The first participants received their diagnoses in February 2015, when we had sequenced around 2,000 whole genomes, with the first diagnosis of children made in January 2016.

As we have moved to 100,000 genomes, the number of people has grown. People like Project participant Alexander and his family who in finally receiving a diagnosis for LEOPARD Syndrome can now finally know what is wrong and seek support from others living with the same disease. Fellow participant, Jessica, and her family discovered that her condition is caused by errors in the SLC2A1 gene that cause ‘Glut1 deficiency syndrome’ – which only affects around 500 people worldwide. Jessica’s diagnosis has opened up the potential for highly tailored treatments.

Beyond 100,000 genomes

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. Whilst the UK is now an acknowledged leader in population genomics, this is a truly global effort – with the potential to bring patient and economic benefit across the world.

The Secretary of State of Health and Social Care’s announcement on 2 October laid out an exciting roadmap for genomic medicine. His words demonstrate the importance of personalised medicine and its ability to continue to deliver cutting edge care within the NHS: “I’m proud to announce we are expanding our 100,000 Genomes Project so that one million whole genomes will now be sequenced by the NHS and the UK Biobank. I’m incredibly excited about the potential for this type of technology to improve the diagnosis and treatment for patients to help people live longer, healthier lives – a vital part of our long-term plan for the NHS.”

The lasting legacy of the 100,000 Genomes Project is the NHS Genomics Medicine Service that began to roll out at the beginning of October 2018. The Project has proven the concept of genomic medicine at scale and built the infrastructure that underpins the GMS. Genomics and the GMS are transformative, poised to change the way future of healthcare is delivered. As we reach the 100,000 genome milestone, we are at a tipping point in medicine that will usher in an era of highly personalised medicine – which may consign generic drugs and treatments to medical history.

Getting to this point has been a demonstration of the power of partnership. We are only here because of the thousands of patients and their families who have placed their trust in a project at the cutting edge of healthcare. Working with them have been many thousands of NHS staff who worked tirelessly to not only deliver the Project, but in many cases, pioneer totally new systems, processes and procedures to ensure that genomic medicine can become part of routine NHS care. And beyond them there is the vast and rich ecosystem of charities, industry partners, funders, government organisations and a host of others. To everyone – we would like to say “thank you”.

Whatever its history and whenever it began, we can be sure that the genomic medicine journey is just beginning – and its future will be an exciting one.

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