Genomics England: Use of data within the National Genomics Research Library (NGRL)

Amendments included in version (v14) are not permitted under this Data Sharing Agreement. V14 permits ongoing processing for the purposes described in v13. V14 is a three year agreement, however data will only to be released for the next six months. This is a pragmatic approach to enable Genomics England to continue accessing data until proposed amendments in v14 are approved.

Summary of processing permitted under v13:

> Processing was permitted for the 100,000 genomes project which was designed to create a new Genomic Medicine Service (GMS) for the NHS. Genomics England also continued to gather and provide genomic and clinical data for this cohort to continue the diagnostic and research aims of the project.

> The following datasets were accessed: Hospital Episode Statistics: Outpatients (HES OP), HES Admitted Patient Care (APC), HES Outpatients (OP), HES Critical Care (CC), HES Accident & Emergency (A&E), Diagnostic Imaging Dataset (DID), Mental Health Minimum Data Set (MHMDS), Mental Health and Learning Disabilities Data Set (MHLDDS), Mental Health Services Data Set (MHSDS), Patient Reported Outcome Measures (PROMs), Civil Registrations of Death and Demographics. Demographics and PROMs data is no longer required and has been destroyed.

> All Genomics research analysis was carried out within the Genomics England Trusted Research Environment (TRE).> Genomics England were permitted to share pseudonymised data under sublicense, including commercially through its Discovery Forum via their TRE.

> The territory of use was worldwide.

> NCRAS and uncurated NCRAS are also available within the TRE to link to the NHS England datasets held under this Agreement using the Study_ID.

> Genomics England is the controller on this Agreement.

> AWS and Lifebit are processors on this Agreement. They provide the technical infrastructure to host the research environment that data is loaded into, and researchers’ access.

> The following special condition was included: “The data controller must remove all those participants from the cohort who have been recruited using the Consultee process, before submitting the cohort to NHS England for data.”

SUMMARY OF CHANGES BETWEEN THE V13 AND V14 DSA.

THE CHANGES BELOW WILL NOT BE PERMITTED UNDER THIS V14 DSA BUT WILL BE INCLUDED IN A FUTURE AMENDMENT:

> Section 5 has been re-written to put the focus on the data being used broadly within the National Genomics Research Library (NGRL), formerly known as the Genomics TRE.

> Detail of the GMS has been added as an example use of the NGRL data.

> The Generations study has been added as an example use of the NGRL data, and with it, identifiers for this new cohort of newborns and their mothers is to be sent to NHS England for linkage.

> Additional consent materials for the NGRL and Generations study have been provided to NHS England for review and inclusion. This is to widen the cohort from only participants of the 100,000 genomes project to also include participants recruited through the GMS or via the Generations study.

> Additional datasets (MSDS and CSDS) have been requested for the Generations cohort only. (to be disseminated under a sister DSA (DARS-NIC-733503-V0X9Q)

***

Genomics England requires access to NHS England Data for use in their National Genomics Research Library (NGRL), which operates as a Trusted Research Environment (TRE).

National Genomic Research Library (NGRL)

The NGRL is a secure national resource of genomic, health and sample data managed by Genomics England, which builds on the research environment created by Genomics England for the 100,000 Genomes Project that completed recruitment in 2018 and involved the sequencing of approximately 100,000 genomes. It contains cohorts of patients/participants recruited via programmes set up for the NHS Genomic Medicine Service (GMS), the 100,000 Genomes Project, and other studies/programmes where patients/participants genomes have been sequenced, and provides a national standardised genomic research resource. Being able to compare all patient data in one place provides researchers with an opportunity to better understand diseases, develop new treatments and can lead to new discoveries. Only research using cohorts covered by this Agreement for the purposes specified can process the NHS England Data.

The following are examples of the aims of the use of data within the NGRL provided by Genomics England:

(1) NHS Genomic Medicine Service (NHS GMS)

Following the successfully delivery of the 100,000 Genomes Project, Genomics England begun work to deliver the NHS GMS. This service will offer patients the dual opportunity of routine clinical care alongside a choice to participate in research spanning across all genomic tests within the NHS, starting with whole genomes. Development of the NHS GMS builds on the evidence generated by the 100,000 Genomes Project, but also extends to other genomic testing other than Whole Genome Sequencing (WGS).

The NHS GMS is led and commissioned by NHS England and will consist of:

> NHS Genomic Laboratory Hubs (GLHs) that will work as part of a National Genomic testing service. The provisions in this service will be determined by a national genomic test directory that outlines the testing strategies and technology to be employed for rare and inherited disease, cancer and other defined conditions/ applications.

> Clinical Genetic Services

> Cancer services using genomic analysis to guide treatment

Within the GMS, two particular cohorts are defined:

(a) The Rare Diseases cohort

The NGRL rare diseases cohort will consist of families with rare diseases, based on family structures appropriate to the provision of the GMS. This will harness the strength of current UK rare disease programmes and will advance current understanding of rare disease mechanisms. It may also impact on common diseases that share similar phenotypes. It will also offer opportunities for biomarker, clinical, and interventional studies through industrial partnerships. Genomics England will actively support the implementation of the UK Rare Disease Strategy. Building on work already undertaken by the 100,000 Genomes Project, this will facilitate the generation of a national data resource of all genomic data, with a focus on WGS but including all genomic testing.

The goals of processing data of patients with rare disease are:

• To increase discovery of pathogenic variants (the gene variant responsible for causing disease) for rare disease.

• To add value with additional biological insights that build confidence in commonly accepted pathogenic variants.

• To enhance the clinical interpretation of WGS in rare disease.

• To develop a programme of functional pathways for genomic tests other than whole genome sequencing, specifically, transcriptomics (the study of all the ribonucleic acid (RNA) molecules within a cell, otherwise known as the transcriptome), epigenetics (the study of how cells control gene activity without changing the DNA sequence), micro RNAs and biomarkers.

• To return findings to the NHS for feedback to patients.

• To create a unique dataset for rare diseases that may enable therapeutic innovation.

(b) The Cancer cohort

The NGRL will continue to learn from and collaborate with other projects who are producing an inventory of genomic, transcriptomic and epigenomic changes in a wide range of different tumour types. Researchers from these projects access the data via an approved sublicensing agreement with Genomics England.

The goals of processing data for patients with cancer are to:

• Use WGS to identify novel driver mutations for cancer and to understand its evolutionary genetic architecture through primary and secondary malignant disease (by multiple biopsy and WGS).

• Partner stratified healthcare programmes and outcome studies with patients from the NHS in England, to enable understanding of WGS benefits in defining predictors of therapeutic response to cancer therapies.

• To use other genomic testing approaches to offer additional biological insights into cancer.

• To utilise WGS to identify new pathways for cancer therapies and improved diagnostic characterisation.

Other forms of collaboration include direct partnerships to develop tools to improve systems and services. For example, partnering with Lifebit to take advantage of their technical genomic data tooling.

(2) Generations Study

Every day, nine babies in the UK are born with a rare genetic condition that could be treated, prevented, or even cured if only it had been diagnosed when those babies were newborns. The Generation Study is aiming to find out if this situation can be improved by recruiting 100,000 newborn babies at NHS Trusts throughout England and conducting WGS to screen for over 200 rare genetic conditions that are treatable in early childhood. It is hoped that babies affected by these conditions will be identified more quickly, treated earlier and therefore have improved clinical outcomes.

The 3 research questions that Genomics England hope to answer are:

1. Can we better diagnose, and therefore care for, children with rare diseases?

2. Can we give researchers opportunities to improve their understanding of rare disease, to develop new treatments, and diagnoses, and better understand how our genes affect our health?

3. Should we, and if so how should we, use a baby’s genome throughout their lifetime as a resource they and their doctors can use if, for example, they become ill as they get older?

Additional processing for the Generation Study involves but is not limited to:

> Identifying discrepancies between WGS interpretation results and Bloodspot data results from the CSDS Dataset. This will be conducted on AWS cloud via an automated system developed by Genomics England. Discrepancies will be reported in the cases interpretation portal to be made available to the treating clinician.

> Evaluation of the cost effectiveness, health related outcomes, demographics monitoring and impact on the NHS. Further details of the outputs are detailed below.

The following NHS England Data will be accessed:

> Hospital Episode Statistics (HES) - these Datasets provide the core clinical data for participants and are vital to the provision of a detailed longitudinal medical history for participants. Specifically, the following HES Datasets are required:

- Admitted Patient Care (APC)

- Accident & Emergency (A&E)

- Critical Care (CC)

- Outpatients (OP)

> Emergency Care Data Set (ECDS) – necessary to understand which patients attend emergency departments and what treatment they receive in order to assess if there are associations with genetic markers.

> Diagnostic Imaging Dataset (DID) – necessary to provide invaluable, detailed information to build on participants’ phenotypes (observable characteristics), e.g., tumour size and spread in cancer, adding to the understanding of patients’ histories on individual and cohort level and their relationship with genomic alterations.

> Mental Health – necessary because the GMS includes recruitment of psychiatric diseases and others with mental health phenotypes: intellectual disability and seizures are expected to be some of the most prevalent conditions within the Project. For the 100,000 genomes project approximately 10% of project participants have a mental health record. Mental health Data are therefore vital in ensuring that a complete and relevant medical history is available for all participants.

> Civil Registration Mortality – necessary because deaths Data is essential for performing survival analyses; this is crucial information for research in combination with other medical history. Knowledge of participant death is also vital for the correct analysis of medical timeline data and for the management of participant cohorts.

> Cancer Registration – necessary because it provides a clinical background for the patient's cancer journey which may help provide scientific and medical insights when compared against the patient's genome.

> MRIS Events Mortality and Demographic Data - still required for open-ended research, specifically for researchers which have already been using this Data and need to go back to it. Losing this Dataset may cause disruption to their research.

> Community Services Data Set (CSDS) – necessary to evaluate the cost effectiveness of the Generation Study, to estimate the impact of WGS in newborns, and identify discrepancies in diseases identified between WGS interpretation results and the CSDS Dataset, which will be reported in the interpretation portal to be made available to the treating clinician.

>Maternity Services Data Set (MSDS) – necessary for discovery research purposes.

The evaluation of WGS data in the context of rich and extended phenotypes derived from electronic health records, such as blood pressure, cholesterol, glucose, and pharmacogenomics (a field of research that studies how a person's genes affect how he or she responds to medications.), adds significant value. The richness of the NGRL datasets will allow Genomics England to move beyond the primary phenotype of the rare disease, cancer or infectious disease that led to the patient’s initial WGS in the context of other continuous traits, diseases and response to therapy including harm.

The level of the Data will be:

> Identifiable

For the following Datasets: HES APC; HES OP; HES A&E; ECDS; Cancer Registration Data; Civil Registrations of Death, many indirect identifiable Data items have been requested because they provide valuable Data that can help researchers make new scientific and medical discoveries. All directly identifiable Data items will either be removed or transformed according to best practice agreed with NHSE. To ensure patients won’t be identified the researchers and their projects are examined before access is granted to the Data, and an agreement to not re-identify patients is signed. Further Genomics England monitors all Data leaving the NGRL and will not allow patient records to be exported.

The Data will be minimised as follows:

> Limited to a study cohort identified by Genomics England, comprising of patients recruited via (1) the 100,000 genomes project who also consented to longitudinal research (~80,000 participants), (2) the Genomics Medicines Service (expected ~100,000 new additions per year) or (3) the Generations Project, which follows newborn babies (expected ~50,000 new additions per year - recruitment is due to begin in Dec 2023 and will continue until 100,000 participants have been recruited in 2025).

> Genomics England will request full history of patient Data to provide maximum insight, and therefore maximum value to the researchers accessing the Data. Because of the wide scope of the proposal, there are no other alternative or less intrusive ways of achieving the purpose described.

Genomics England is the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above. Genomics England also process the Data.

NHS England has commissioned Genomics England to undertake the work. NHS England does not specify what Data are required to deliver the work nor how the Data shall be processed to achieve that purpose. Such decisions are taken by Genomics England.

The lawful basis for processing personal data under the UK GDPR is:

> Article 6(1)(f) - processing is necessary for the purposes of the legitimate interests pursued by the controller or by a third party.

Genomics England has determined the processing is necessary for its legitimate interests in carrying out medical research on the causes, diagnosis and treatment of rare diseases and cancers.

The lawful basis for processing special category data under the UK GDPR is:

> Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

It is necessary for Genomics England to process special category participant data for carrying out medical research on the causes, diagnosis and treatment of rare diseases and cancers, which is expected to benefit patients.

The funding is provided by the Department of Health and Social Care. The funding is specifically for the projects described. Funding is in place until March 2025, with the intention to renew this funding periodically.

The funder will have no ability to suppress or otherwise limit the publication of findings.

Lifebit provides IT support to Genomics England.

Amazon Web Services (AWS) provides IT back up services to Genomics England and will store copies of the Data as contracted by Genomics England.

Representatives from patient and public bodies have an important role to play in Genomics England commercial initiatives. These representatives ensure transparency is upheld, and the interest of those whose data is being used is always being respected.

In the early stages of the Library, Genomics England undertook a range of work to ensure that potential participant’s views were included in the formulation of the ethical policies submitted for research ethics approval and in the development of patient information. The views of different groups of potential participants (those affected by cancer, rare disease, and those from BAME communities) in relation to ethical issues raised by the 100,000 Genomes Project were sought and findings were published on the Genomics England website (See all reports under ‘patient and public involvement - https://www.genomicsengland.co.uk/library-and-resources/ and the Genomics England Engagement Strategy). Genomics England will continue to engage with these stakeholders. Further to this, each of the 13 currently recruiting NHS Genomic Medicine Centres had dedicated Patient and Public Involvement leads (PPI) who are responsible for engaging with and involving local potential participant groups from diverse backgrounds. It is expected that the future NHS GMS will continue these local PPI activities to shape and inform the service.

A Participant Panel has also been established. This 30-strong group has provided invaluable advice on a range of topics, for instance, in shaping how analysis is monitored, how results are returned, and how advice and support should be framed. Participant Panel members have either donated samples to the Library themselves or are carers of participants. They take part in a wide variety of consultative groups, such as the Genomics England Ethics Advisory Committee but most importantly are guardians of the dataset, with representatives on the Access Review Committee. Participants play an important part in every decision made about access to data.

SUB-LICENCING:

Genomics Clinical Interpretation Partners (GeCIP) members (Academic research organisations), and members of the Discovery Forum (Commercial organisations) will also have access to the pseudonymised Data within the NGRL, subject to internal approval by Genomics England. NHS England Data is combined with the genomic and sample data within the NGRL, providing a more comprehensive medical history, and going forward, a more comprehensive patient journey which will be a valuable resource for medical research. All applications have to provide health and social care benefits and are reviewed by a panel (the Access Review Committee (ARC)) before access is granted.

It is anticipated that the volume of sub-licences will be 150-200 per year. The GeCIP sub licence agreement is indefinite, until it is terminated by either the GeCIP member or Genomics.

The Data Access Agreement for Discovery Forum Members has a specified term, normally 12 months, at which point the company and Genomics can choose to renew or not.

All requests for data access will be subject to the following considerations:

• Protection of data subjects (honouring commitments made to them, acting within the scope of consent and according to conditions of Research Ethics Committee approval).

• Compliance with legal and regulatory requirements General Data Protection Regulation 2018, Data Protection Bill 2017, Freedom of Information Act 2000, NHS Act 2006, Health and Social Care Act 2012, the Common Law Duty of Confidentiality, Human Tissue Act 2004 and applicable requirements from organisations affiliated with the Health Research Authority, including Research Ethics Committees and the Confidentiality Advisory Group (CAG).

• Provision of a signed Genomics England data access agreement to the Access Review Committee.

• Prioritisation of access according to resource availability.

• Facilitation of high-quality health research

Commercial partnerships are crucial to achieving the aims of the NGRL and are achieved through the Discovery Forum. As with the non-commercial academic research led by GeCIP, commercial research aims to bring benefit to the patients and, through the use of the Data, inform development of platforms and tools for future diagnostic discovery. Commercial research can be broadly categorised into four themes that answer different questions along the typical Research and Discovery Biopharmaceutical Pipeline. At a high level they are divided into:

• Diagnostic discovery

• Pre-clinical research

• Clinical Trials Referral

• Real World Evidence / Market Access

Approval process for Commercial organisations for access to the NGRL:

Discovery Forum applications from a commercial organisation would be reviewed for suitability by the Partnership Development (PD)Team. The PD Team consider the credentials of the applying organisation including consideration of adverse public perception and reputational risk from approving data access for that organisation. If the PD Team feel appropriate, they are then passed on to be scrutinised by the independent Access Review Committee (ARC). ARC is constituted of Participant Panel members and senior individuals from various scientific and medical backgrounds. ARC assess the company’s research proposal, including patient/participant involvement, potential future value to patients/the NHS and the ethics of the proposal.

The ARC will assess whether there has been any Patient and Public Involvement and Engagement (PPIE) informing the research questions and design. For many commercial applications that are exploring early-stage research and development (R&D), for example, target identification and validation, there will not have been any PPIE because the research may be tied to exploring fundamental biological mechanisms and pathways rather than particular conditions or phenotypes. If there has been PPIE, the ARC will determine whether it has adequately informed the research questions and design, and whether there is a commitment to ongoing PPIE and transparency following the outcomes of the research. Although PPIE is not a requirement of applications, ARC encourage applicants to consider at what stage in their R&D process it would be appropriate to consult with patient advocacy and participation groups.

Genomics England will only work with companies that are aligned with its strategy and mission to bring the benefits of genomic medicine to everyone. The Partnerships Development team will assess whether a company seeking access to NGRL data is working in the cancer or rare disease diagnostics and therapeutics space, or supporting UK Government strategic scientific initiatives – if not, Genomics England would not permit an application to ARC in the first place. All applications must conform to the acceptable uses set out in the REC-approved NGRL protocol. If the research proposal is for later stage research that has a clear pathway to intended patient or health system benefit, the ARC would expect to see this articulated as part of the rationale for seeking access to NGRL data. Given the early stage of much commercial genomics research, not all accepted applications will be able to demonstrate a clear explanation of the expected healthcare benefits.

Approval process for GeCIP users (academic) of the NGRL:

• Researcher visits Genomics England website to enrol as a GECIP member

• Completion of onboarding process; Verification by their institution (institution will be required to sign a Genomics participation agreement and appoint a membership secretary), verification of their self-stated qualifications and areas of research interest by the GEL Scientific Manager to join their domain of choice, take the IG and GECIP rules training course and pass test with at least 80%. They are then able to access the NGRL and the Research Portal (the area where prospective GeCIP applicants can apply and register their research project)

• Within 3 months of gaining access they need to either submit a research proposal for Genomics England approval, which currently has to fit with the Detailed Research Plan for their domain, or join another registered project. Otherwise they will lose access.

• On an annual basis, complete a survey sent out by Genomics England giving details of their research progress and any outputs, to aid reporting to ARC.

• Any data they wish to either import or export to/from the NGRL has to be approved by Airlock (Airlock policy is described below) as not being personally identifiable.

• If a researcher has not accessed the NGRL, the Research Portal, or logged into their GEL account to gain access to either of the previous for 6 months their account will be deactivated.

All research activities undertaken in the NGRL aim to enrich the existing dataset via one or multiple routes:

• Identification of diagnoses originally missed by the standardised pipeline

• Feedback of new diagnoses to patients

• Mobilising samples which can help to identify diagnoses that were missed through analyses of WGS alone

Researchers can access pseudonymised Data through NGRL under sub licence. The only Data allowed to be exported are summary results. An airlock policy has been established which enables material (data, files, tools etc) to be moved in or out of the NGRL in a controlled and supervised manner; facilitating research and discovery, while maintaining control of security and access.

Data accessed under sub licence is only granted to named individuals identified to Genomics England who agree to comply with the Airlock policy, Information Governance and IT Security Policy. Before being provided with credentials necessary to access the NGRL a Company Researcher must complete information governance training which shall be provided by Genomics England.

AIRLOCK POLICY:

The following rules are applied to all airlock requests:

1. All relevant details of the summary results to be transferred must be provided with every request.

2. All summary results transferred must be checked by Genomics England to ensure compliance with the relevant policies. Users will be notified of any summary results rejected along with the reason for the rejection.

3. All imports will be checked for viruses and malware and those failing this test will be rejected. It is the responsibility of the requestors to resolve such issues before re-submitting the file for transfer.

4. Summary results requested for transfer are assessed using the following criteria:

a. whether the request aligns with the users ARC approval in full;

b. whether the request can clearly be demonstrated to be aligned with a registered project in the NGRL;

c. any data security implications;

d. any disclosure risks;

e. the technical feasibility and associated cost of the request;

f. when importing data, its scientific value to the community of researchers within the NGRL, and when and how it will be shared;

g. when importing data, checks will be performed to ensure that the data importer owns the data and holds the correct consents and approvals.

The Airlock Manager has formal delegated approval to approve requests where there is precedent from previous Airlock Review Committees. For more complicated requests or where no precedent has been set these will go to the airlock committee for review and a decision. The airlock committee is a delegation of the Genomics England Chief Scientist who responsible for oversight of all airlock requests in accordance with the airlock policy. The committee comprises of:

• Technical Lead

• User Community Representative

• Bioinformatics Director

• Caldicott Guardian

• Chief Scientist representative

The Data will be processed worldwide.

Access is restricted to substantive employees of Genomics England, Genomics Clinical Interpretation Partners (GeCIP) members, and members of the Discovery Forum, who have authorisation from the Principal Investigator.

GeCIP membership is open to any individual, student or member of staff, who is affiliated with a host institution which include the following:

• UK academic research institutions (e.g., universities, research institutions etc.)

• NHS trusts or authorities

• UK and foreign charitable organisations directly related to the focus of the 100,000 Genomes Project

• Foreign universities and research institutions that carry out significant research activity

• UK and foreign governmental departments that carry out significant research activity (e.g., Medical Research Council (MRC), National Institute of Health (NIH), Public Health England (PHE))

• Foreign healthcare organisations (private or public) that undertake significant research activity

To be eligible for data access as a GeCIP member, applicants must meet these requirements:

• Their host institution has signed a GeCIP Participation Agreement, which outlines the key principles that members of each institution must adhere to, including the Intellectual Property and Publication Policy.

• Their host institution has verified that they are affiliated with that institution.

• The applicant’s GeCIP domain has submitted a detailed research plan and it has been approved by the Genomics England Access Review Committee (see below).

• The GeCIP domain lead has approved the application.

• Following approval, GeCIP researchers must sign a specific agreement (‘GeCIP rules’) covering their behaviour and working practice within the data infrastructure.

• Data access will not then be granted until a researcher has successfully passed mandatory information governance training.

All applications have to provide health and social care benefits in England and are reviewed by a panel (the Access Review Committee (ARC)).

The ARC provides an independent examination of requests for data access. The ARC comprises external scientific experts, patient representatives and members of Genomics England’s Participant Panel.

GeCIP users will be granted access to all data and knowledge held within the NGRL. Each GeCIP domain will have access to its own private shared area of the NGRL for data storage and collaboration. The secure virtual desktop infrastructure will provide the ‘workspace’ for clinical teams, research groups and trainees to undertake their work.

All personnel accessing the Data have been appropriately trained in data protection and confidentiality.

The Data will be linked at person record level with the patient’s genetic data within the NGRL. This includes the following data:

> National Cancer Registration and Analysis Service (NCRAS)

and uncurated NCRAS data

> Secure Anonymised Information Linkage (SAIL) data; Welsh data

> Patient samples (e.g., blood, saliva, tissue, RNA, plasma and serum)

> NHS Trusts data

The Data will not be linked with any other data.

The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised Dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised Dataset.

To protect patient confidentiality, access to the NGRL will be granted only for specific, approved purposes in accordance with informed consent. Any attempted use beyond the specified purpose may lead to exclusion and possible legal action, where appropriate.

Data accessed under sub licence will not be re-identified.

Genomics England rely on GDPR Article 6 (1)(f) for the personal data and Article 9(2)(j) for the special category data shared within the NGRL.

Data shared through the Airlock process is aggregate data only and is therefore not personal data so does not require a legal basis under the UK GDPR.

A release register detailing any sub licences and onward sharin

Researchers will have their own dissemination and communication strategies, however a full list of scientific publications and conferences/posters will be made available on the Genomics England website on an ongoing basis. The expected outputs of the processing will be:

> Submissions to peer reviewed journals

> Presentations at conferences

> Posters

> Creation of a database of all genomic data, including all genomic and omics tests.

The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the Dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

> Journals

> Posters

> Website: A list of publications is kept up-to-date on the Genomics website: https://www.genomicsengland.co.uk/research/publications?

> Presentations at appropriate conferences

> Upload of findings onto the ‘Discovery Forum’: Genomics England works with industry partners through the Discovery Forum. All members of the Forum are obliged to publish all findings and research at the point at which intellectual property for any product is protected. Additionally, it allows the NGRL users to report back to Genomics England on what aspects of the data are proving to be most useful to their research studies, what data is missing and how the data should be collected and developed. These partners act as a critical friend and have already made many helpful suggestions to increase the likelihood of successful research in the future for all those using Genomics England's NGRL.

A number of benefits have already been yielded from the use of the NHS England Data held under this Agreement:

• Patient benefit: providing clinical diagnosis and in time, new or more effective treatments for NHS patients. The project found that using WGS led to a new diagnosis for 25% of the participants. Of these new diagnoses, 14% found variations in regions of the genome that would be missed by other methods, including other types of non-whole genomic tests.

• New scientific insights and discovery: with the consent of patients, creating a database of 100,000 whole genome sequences linked to continually updated long term patient health and personal information for analysis by researchers. This has enhanced genomic healthcare research by creating the largest genomic healthcare data resource in the world, which in turn will uncover answers for participants both now and in the future through genomic-level analysis of conditions.

• Accelerating the uptake of genomic medicine in the NHS: working with NHSE and other partners to deliver a scale-able WGS and informatics platform to enable these services to be made widely available for NHS patients. In addition, through the Genomics England Clinical Interpretation Partnership (GeCIP), creating a mechanism to both continually improve the accuracy and reliability of information fed back to patients and add to knowledge of the genetic basis of disease. This acceleration significantly contributed to delivering the Genomics Medicine Service (GMS) for the NHS, which makes whole genome sequencing part of routine healthcare.

• Stimulating and enhancing UK industry and investment: by providing access to this unique data resource by industry for the purpose of developing new knowledge, methods of analysis, medicines, diagnostics and devices. The creation of the Discovery Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape.

• Increasing public knowledge and support for genomic medicine: delivering an ethical and transparent programme which has public trust and confidence and working with a range of partners to increase knowledge of genomics. After involving participants in all stages of the pioneering 100,000 Genomes Project and putting a trusted system in place contributed to a major dialogue led by Ipsos MORI and commissioned by Genomics England and co-funded by UK Research and Innovation’s Sciencewise programme in 2019 (post 100,000 genomes project completion) found the public are enthusiastic and optimistic about the potential for genomic medicine.

A genome is the body’s instruction manual - a copy is stored in almost every healthy cell in your body. The study of that genome and all the technologies needed to analyse and interpret it is called genomics.

Genomics England was established by the Department of Health to deliver the 100,000 Genomes Project. This followed the announcement in December 2012 by the Prime Minister of a programme of whole genome sequencing (WGS) as part of the UK Government’s Life Sciences Strategy. The principal objective of the 100,000 Genomes Project was to sequence 100,000 genomes from participants with cancer and rare disorders, and to link the sequence data to a standardised, extensible account of diagnosis, treatment, and outcomes gathered at recruitment, but primarily through the ongoing collection of medical records.

Combining genomic sequence data with medical records has created a ground-breaking research resource. Researchers are currently studying how best to use genomics in healthcare and how best to interpret the data to help patients. The causes, diagnosis and treatment of disease is also being investigated. Revealing which variants cause disease is also helping companies find new targeted medicines. Kick-starting a UK genomics industry was another key aim of the project and the UK now has a vibrant genomics ecosystem.

The project was designed to create a new genomic medicine service for the NHS. It was also designed to create new capability for the clinical genomics research, both academic and industrial, through the creation of a unique medical data set combining genomic sequence data with medical records within a secure research infrastructure.

Genomics England has sought to obtain information from participants’ medical records that span their entire lifetime. The DNA sequence, and information from patients’ health records and provided by the participants, are collected and stored securely as a resource for use by approved researchers for scientific and medical purposes during the life, and after the death, of participants. Diagnoses arising from the sequencing and analysis of the participants’ DNA are being fed back to participants: for many they are receiving a diagnosis for the first time.

The way in which the NHS is able to link a whole lifetime of medical records with a person’s genome data and the fact it can do this on a large scale is unique. The richness of this data can help to understand disease and to tease apart the complex relationship between our genes, what happens to us in our lives and illness.

The richness of the high-quality data sets is crucial to the success of the 100,000 Genomes Project in delivering value to the NHS. The evaluation of WGS data in the context of rich and extended phenotypes derived from electronic health records adds significant value. The richness of the Project dataset allows Genomics England to move beyond the primary phenotype that led to the patient’s enrolment to evaluate the genome sequence in the context of other continuous traits, diseases and responses to therapy.

The 100,000 Genomes Project completed recruitment of rare disease participants and cancer patients in early 2019.

Genomics England will now continue to gather and provide genomic and clinical data for this cohort to continue the diagnostic and research aims of the project.

To achieve these goals Genomics wish to continue to access the following datasets:

Hospital Episode Statistics: Outpatients, Admitted Patient Care, Critical Care and Accident & Emergency. These datasets provide the core clinical data for participants and are vital to the provision of a detailed medical history for participants.

Diagnostic Imaging Dataset. This provides invaluable, detailed information to build on participants’ phenotypes, e.g. tumour size and spread in cancer, adding to the understanding of patients’ histories on individual and cohort level and their relationship with genomic alterations.

Mental Health Data sets: Minimum Data Set, Mental Health and Learning Disabilities Data Set, and Mental Health Services Data Set. The 100,000 Genomes Project includes recruitment of psychiatric diseases and others with mental health phenotypes: intellectual disability and seizures are some of the most prevalent conditions within the Project. To-date nearly 10% of project participants have a mental health record. Mental health data are therefore vital in ensuring that a complete and relevant medical history is available for all participants.

Patient Reported Outcome Measures (PROMS). In combination with other data, this dataset allows correlation of outcomes and pain related measures to genetic markers and interventions in some key diseases. More generally they have utility in non-hypothesis driven research, including research into electronic health records.

Mortality data are essential for performing survival analyses: this is crucial information for research in combination with other medical history. Cause of death information is vital in order to determine if mortality is related to the primary disease of a participant or to highlight unforeseen trends. Knowledge of participant death is also vital for the correct analysis of medical timeline data and for the management of participant cohorts.

Demographic Data: These identifiable data sets are vital for the safe and efficient management of the participant cohort. They are used to ensure that Genomics' data applications are correct, do not cover duplicate participants, that withdrawn participants are excluded from data collection, and that participants’ details are accurate.

Genomics England works with industry through its Discovery Forum. The Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape. Industry partners comprise pharmaceutical, biotech and diagnostic companies, and those specialising in laboratory and data analysis. These companies have joined the Forum to work in a pre-competitive environment with access to a selection of genomic and associated clinical data. Ultimately, the Discovery Forum aims to help the 100,000 Genomes Project and its partners to turn research findings into treatments, diagnostics and benefits for patients as soon as possible. There are currently over 100 members of the Forum.

As the Discovery Forum is a collaborative venture, no fees are levied on participating organisations. All members of the Forum are obliged to publish all findings and research at the point at which intellectual property for any product is protected. Participants in the 100,000 Genomes Project have been asked explicitly to give consent for commercial companies to access their pseudonymised genome and health data.

The Forum was created in July 2017 and allows industrial partners to report back to Genomics England on what aspects of the data are proving to be most useful to their research studies, what data is missing and how the data should be collected and developed further so it is captures what industry needs, in a format that is compatible with their research and data systems. These partners act as a ‘critical friend’ and have made many helpful suggestions to increase the likelihood of successful research in the future for all those using Genomics England’s landmark data set.

The lawful basis for processing participant data under the General Data Protection Regulation (GDPR) used by Genomics England is Legitimate Interests as set out under Article 6(1)(f) of the GDPR. It is necessary for Genomics England to process Participant Data for its legitimate interests in carrying out medical research and in providing reports used by clinicians in their care of participants.

The processing is necessary to support and enable Genomics England's legitimate interests in enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancers.

The processing is necessary to support and enable Genomics England’s legitimate interests in:

· Creating a new genomic medicine service for the NHS (not a part of this agreement - will be part of a future amendment)

· Enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancer.

Patients and participants will be at the heart of this programme and include the participant panel, a 30 strong panel involved in Genomics England research committees.

The beneficiaries are:

· Participants through the work we do will influence their care;

· researchers and industry by giving them access to a unique ground-breaking resource of genomic data combined with life-course clinical data;

· and the wider public by accelerating the uptake of genomic medicine making it available to patients in the UK.

Specific outputs for Genomics England are to continue to release updated genomic and clinical data into the TRE to support this ongoing research. Each research group who accesses this data will have their own defined output strategy and expectations which they will aim to deliver against. A full list of scientific publications and conferences/posters can be found on the Genomics England website. Recent specific examples of journal outputs are as follows:

- A systematic analysis of splicing variants identifies new diagnoses in the 100,000 Genomes Project. Alexander J.M. Blakes, Htoo Wai, Ian Davies, et al. Genome Medicine Jul 2022 DOI: 10.1186/s13073-022-01087-x. This demonstrated the clinical value of examining non-canonical splicing variants in individuals with unsolved rare diseases by identifying 35 new likely diagnoses from 258 probands with an unsolved rare disease.

- Prognosis and oncogenomic profiling of patients with tropomyosin receptor kinase fusion cancer in the 100,000 genomes project. John Bridgewater, Xiaolong Jiao, Mounika Parimi, et al. Cancer Treatment and Research Communications Aug 2022 DOI: 10.1016/j.ctarc.2022.100623. This study supports the hypothesis that Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are primary oncogenic drivers and the co-occurrence of NTRK gene fusions with other oncogenic alterations is rare. Overall survival was not statistically significant between NTRK and non-NTRK tumour patients.

- Participant experiences of genome sequencing for rare diseases in the 100,000 Genomes Project: a mixed methods study. Michelle Peter, Jennifer Hammond, Saskia C. Sanderson, et al. European Journal of Human Genetics Mar 2022 DOI: https://doi.org/10.1038/s41431-022-01065-2. This study highlights how expectation-setting is critical when offering genome sequencing, and that post-test counselling is important regardless of the GS result received, with parents perhaps needing additional emotional support.

• Patient benefit: providing clinical diagnosis and in time, new or more effective treatments for NHS patients. The project found that using WGS led to a new diagnosis for 25% of the participants. Of these new diagnoses, 14% found variations in regions of the genome that would be missed by other methods, including other types of non-whole genomic tests.

• New scientific insights and discovery: with the consent of patients, creating a database of 100,000 whole genome sequences linked to continually updated long term patient health and personal information for analysis by researchers. This has enhanced genomic healthcare research by creating the largest genomic healthcare data resource in the world, which in turn will uncover answers for participants both now and in the future through genomic-level analysis of conditions.

• Accelerating the uptake of genomic medicine in the NHS: working with NHSE and other partners to deliver a scale-able WGS and informatics platform to enable these services to be made widely available for NHS patients. In addition, through the Genomics England Clinical Interpretation Partnership (GeCIP), creating a mechanism to both continually improve the accuracy and reliability of information fed back to patients and add to knowledge of the genetic basis of disease. This acceleration significantly contributed to delivering the Genomics Medicine Service (GMS) for the NHS, which makes whole genome sequencing part of routine healthcare.

• Stimulating and enhancing UK industry and investment: by providing access to this unique data resource by industry for the purpose of developing new knowledge, methods of analysis, medicines, diagnostics and devices. The creation of the Discovery Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape.

• Increasing public knowledge and support for genomic medicine: delivering an ethical and transparent programme which has public trust and confidence and working with a range of partners to increase knowledge of genomics. After involving participants in all stages of the pioneering 100,000 Genomes Project and putting a trusted system in place contributed to a major dialogue led by Ipsos MORI and commissioned by Genomics England and co-funded by UK Research and Innovation’s Sciencewise programme in 2019 (post 100,000 genomes project completion) found the public are enthusiastic and optimistic about the potential for genomic medicine.

A genome is the body’s instruction manual - a copy is stored in almost every healthy cell in your body. The study of that genome and all the technologies needed to analyse and interpret it is called genomics.

Genomics England was established by the Department of Health to deliver the 100,000 Genomes Project. This followed the announcement in December 2012 by the Prime Minister of a programme of whole genome sequencing (WGS) as part of the UK Government’s Life Sciences Strategy. The principal objective of the 100,000 Genomes Project was to sequence 100,000 genomes from participants with cancer and rare disorders, and to link the sequence data to a standardised, extensible account of diagnosis, treatment, and outcomes gathered at recruitment, but primarily through the ongoing collection of medical records.

Combining genomic sequence data with medical records has created a ground-breaking research resource. Researchers are currently studying how best to use genomics in healthcare and how best to interpret the data to help patients. The causes, diagnosis and treatment of disease is also being investigated. Revealing which variants cause disease is also helping companies find new targeted medicines. Kick-starting a UK genomics industry was another key aim of the project and the UK now has a vibrant genomics ecosystem.

The project was designed to create a new genomic medicine service for the NHS. It was also designed to create new capability for the clinical genomics research, both academic and industrial, through the creation of a unique medical data set combining genomic sequence data with medical records within a secure research infrastructure.

Genomics England has sought to obtain information from participants’ medical records that span their entire lifetime. The DNA sequence, and information from patients’ health records and provided by the participants, are collected and stored securely as a resource for use by approved researchers for scientific and medical purposes during the life, and after the death, of participants. Diagnoses arising from the sequencing and analysis of the participants’ DNA are being fed back to participants: for many they are receiving a diagnosis for the first time.

The way in which the NHS is able to link a whole lifetime of medical records with a person’s genome data and the fact it can do this on a large scale is unique. The richness of this data can help to understand disease and to tease apart the complex relationship between our genes, what happens to us in our lives and illness.

The richness of the high-quality data sets is crucial to the success of the 100,000 Genomes Project in delivering value to the NHS. The evaluation of WGS data in the context of rich and extended phenotypes derived from electronic health records adds significant value. The richness of the Project dataset allows Genomics England to move beyond the primary phenotype that led to the patient’s enrolment to evaluate the genome sequence in the context of other continuous traits, diseases and responses to therapy.

The 100,000 Genomes Project completed recruitment of rare disease participants and cancer patients in early 2019.

Genomics England will now continue to gather and provide genomic and clinical data for this cohort to continue the diagnostic and research aims of the project.

To achieve these goals Genomics wish to continue to access the following datasets:

Hospital Episode Statistics: Outpatients, Admitted Patient Care, Critical Care and Accident & Emergency. These datasets provide the core clinical data for participants and are vital to the provision of a detailed medical history for participants.

Diagnostic Imaging Dataset. This provides invaluable, detailed information to build on participants’ phenotypes, e.g. tumour size and spread in cancer, adding to the understanding of patients’ histories on individual and cohort level and their relationship with genomic alterations.

Mental Health Data sets: Minimum Data Set, Mental Health and Learning Disabilities Data Set, and Mental Health Services Data Set. The 100,000 Genomes Project includes recruitment of psychiatric diseases and others with mental health phenotypes: intellectual disability and seizures are some of the most prevalent conditions within the Project. To-date nearly 10% of project participants have a mental health record. Mental health data are therefore vital in ensuring that a complete and relevant medical history is available for all participants.

Patient Reported Outcome Measures (PROMS). In combination with other data, this dataset allows correlation of outcomes and pain related measures to genetic markers and interventions in some key diseases. More generally they have utility in non-hypothesis driven research, including research into electronic health records.

Mortality data are essential for performing survival analyses: this is crucial information for research in combination with other medical history. Cause of death information is vital in order to determine if mortality is related to the primary disease of a participant or to highlight unforeseen trends. Knowledge of participant death is also vital for the correct analysis of medical timeline data and for the management of participant cohorts.

Demographic Data: These identifiable data sets are vital for the safe and efficient management of the participant cohort. They are used to ensure that Genomics' data applications are correct, do not cover duplicate participants, that withdrawn participants are excluded from data collection, and that participants’ details are accurate.

Genomics England works with industry through its Discovery Forum. The Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape. Industry partners comprise pharmaceutical, biotech and diagnostic companies, and those specialising in laboratory and data analysis. These companies have joined the Forum to work in a pre-competitive environment with access to a selection of genomic and associated clinical data. Ultimately, the Discovery Forum aims to help the 100,000 Genomes Project and its partners to turn research findings into treatments, diagnostics and benefits for patients as soon as possible. There are currently over 100 members of the Forum.

As the Discovery Forum is a collaborative venture, no fees are levied on participating organisations. All members of the Forum are obliged to publish all findings and research at the point at which intellectual property for any product is protected. Participants in the 100,000 Genomes Project have been asked explicitly to give consent for commercial companies to access their pseudonymised genome and health data.

The Forum was created in July 2017 and allows industrial partners to report back to Genomics England on what aspects of the data are proving to be most useful to their research studies, what data is missing and how the data should be collected and developed further so it is captures what industry needs, in a format that is compatible with their research and data systems. These partners act as a ‘critical friend’ and have made many helpful suggestions to increase the likelihood of successful research in the future for all those using Genomics England’s landmark data set.

The lawful basis for processing participant data under the General Data Protection Regulation (GDPR) used by Genomics England is Legitimate Interests as set out under Article 6(1)(f) of the GDPR. It is necessary for Genomics England to process Participant Data for its legitimate interests in carrying out medical research and in providing reports used by clinicians in their care of participants.

The processing is necessary to support and enable Genomics England's legitimate interests in enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancers.

The processing is necessary to support and enable Genomics England’s legitimate interests in:

· Creating a new genomic medicine service for the NHS (not a part of this agreement - will be part of a future amendment)

· Enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancer.

Patients and participants will be at the heart of this programme and include the participant panel, a 30 strong panel involved in Genomics England research committees.

The beneficiaries are:

· Participants through the work we do will influence their care;

· researchers and industry by giving them access to a unique ground-breaking resource of genomic data combined with life-course clinical data;

· and the wider public by accelerating the uptake of genomic medicine making it available to patients in the UK.

Specific outputs for Genomics England are to continue to release updated genomic and clinical data into the TRE to support this ongoing research. Each research group who accesses this data will have their own defined output strategy and expectations which they will aim to deliver against. A full list of scientific publications and conferences/posters can be found on the Genomics England website. Recent specific examples of journal outputs are as follows:

- A systematic analysis of splicing variants identifies new diagnoses in the 100,000 Genomes Project. Alexander J.M. Blakes, Htoo Wai, Ian Davies, et al. Genome Medicine Jul 2022 DOI: 10.1186/s13073-022-01087-x. This demonstrated the clinical value of examining non-canonical splicing variants in individuals with unsolved rare diseases by identifying 35 new likely diagnoses from 258 probands with an unsolved rare disease.

- Prognosis and oncogenomic profiling of patients with tropomyosin receptor kinase fusion cancer in the 100,000 genomes project. John Bridgewater, Xiaolong Jiao, Mounika Parimi, et al. Cancer Treatment and Research Communications Aug 2022 DOI: 10.1016/j.ctarc.2022.100623. This study supports the hypothesis that Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are primary oncogenic drivers and the co-occurrence of NTRK gene fusions with other oncogenic alterations is rare. Overall survival was not statistically significant between NTRK and non-NTRK tumour patients.

- Participant experiences of genome sequencing for rare diseases in the 100,000 Genomes Project: a mixed methods study. Michelle Peter, Jennifer Hammond, Saskia C. Sanderson, et al. European Journal of Human Genetics Mar 2022 DOI: https://doi.org/10.1038/s41431-022-01065-2. This study highlights how expectation-setting is critical when offering genome sequencing, and that post-test counselling is important regardless of the GS result received, with parents perhaps needing additional emotional support.

• Patient benefit: providing clinical diagnosis and in time, new or more effective treatments for NHS patients. The project found that using WGS led to a new diagnosis for 25% of the participants. Of these new diagnoses, 14% found variations in regions of the genome that would be missed by other methods, including other types of non-whole genomic tests.

• New scientific insights and discovery: with the consent of patients, creating a database of 100,000 whole genome sequences linked to continually updated long term patient health and personal information for analysis by researchers. This has enhanced genomic healthcare research by creating the largest genomic healthcare data resource in the world, which in turn will uncover answers for participants both now and in the future through genomic-level analysis of conditions.

• Accelerating the uptake of genomic medicine in the NHS: working with NHSE and other partners to deliver a scale-able WGS and informatics platform to enable these services to be made widely available for NHS patients. In addition, through the Genomics England Clinical Interpretation Partnership (GeCIP), creating a mechanism to both continually improve the accuracy and reliability of information fed back to patients and add to knowledge of the genetic basis of disease. This acceleration significantly contributed to delivering the Genomics Medicine Service (GMS) for the NHS, which makes whole genome sequencing part of routine healthcare.

• Stimulating and enhancing UK industry and investment: by providing access to this unique data resource by industry for the purpose of developing new knowledge, methods of analysis, medicines, diagnostics and devices. The creation of the Discovery Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape.

• Increasing public knowledge and support for genomic medicine: delivering an ethical and transparent programme which has public trust and confidence and working with a range of partners to increase knowledge of genomics. After involving participants in all stages of the pioneering 100,000 Genomes Project and putting a trusted system in place contributed to a major dialogue led by Ipsos MORI and commissioned by Genomics England and co-funded by UK Research and Innovation’s Sciencewise programme in 2019 (post 100,000 genomes project completion) found the public are enthusiastic and optimistic about the potential for genomic medicine.

A genome is the body’s instruction manual - a copy is stored in almost every healthy cell in your body. The study of that genome and all the technologies needed to analyse and interpret it is called genomics.

Genomics England was established by the Department of Health to deliver the 100,000 Genomes Project. This followed the announcement in December 2012 by the Prime Minister of a programme of whole genome sequencing (WGS) as part of the UK Government’s Life Sciences Strategy. The principal objective of the 100,000 Genomes Project was to sequence 100,000 genomes from participants with cancer and rare disorders, and to link the sequence data to a standardised, extensible account of diagnosis, treatment, and outcomes gathered at recruitment, but primarily through the ongoing collection of medical records.

Combining genomic sequence data with medical records has created a ground-breaking research resource. Researchers are currently studying how best to use genomics in healthcare and how best to interpret the data to help patients. The causes, diagnosis and treatment of disease is also being investigated. Revealing which variants cause disease is also helping companies find new targeted medicines. Kick-starting a UK genomics industry was another key aim of the project and the UK now has a vibrant genomics ecosystem.

The project was designed to create a new genomic medicine service for the NHS. It was also designed to create new capability for the clinical genomics research, both academic and industrial, through the creation of a unique medical data set combining genomic sequence data with medical records within a secure research infrastructure.

Genomics England has sought to obtain information from participants’ medical records that span their entire lifetime. The DNA sequence, and information from patients’ health records and provided by the participants, are collected and stored securely as a resource for use by approved researchers for scientific and medical purposes during the life, and after the death, of participants. Diagnoses arising from the sequencing and analysis of the participants’ DNA are being fed back to participants: for many they are receiving a diagnosis for the first time.

The way in which the NHS is able to link a whole lifetime of medical records with a person’s genome data and the fact it can do this on a large scale is unique. The richness of this data can help to understand disease and to tease apart the complex relationship between our genes, what happens to us in our lives and illness.

The richness of the high-quality data sets is crucial to the success of the 100,000 Genomes Project in delivering value to the NHS. The evaluation of WGS data in the context of rich and extended phenotypes derived from electronic health records adds significant value. The richness of the Project dataset allows Genomics England to move beyond the primary phenotype that led to the patient’s enrolment to evaluate the genome sequence in the context of other continuous traits, diseases and responses to therapy.

The 100,000 Genomes Project completed recruitment of rare disease participants and cancer patients in early 2019.

Genomics England will now continue to gather and provide genomic and clinical data for this cohort to continue the diagnostic and research aims of the project.

To achieve these goals Genomics wish to continue to retain the following datasets:

Hospital Episode Statistics: Outpatients, Admitted Patient Care, Critical Care and Accident & Emergency. These datasets provide the core clinical data for participants and are vital to the provision of a detailed medical history for participants.

Diagnostic Imaging Dataset. This provides invaluable, detailed information to build on participants’ phenotypes, e.g. tumour size and spread in cancer, adding to the understanding of patients’ histories on individual and cohort level and their relationship with genomic alterations.

Mental Health Data sets: Minimum Data Set, Mental Health and Learning Disabilities Data Set, and Mental Health Services Data Set. The 100,000 Genomes Project includes recruitment of psychiatric diseases and others with mental health phenotypes: intellectual disability and seizures are some of the most prevalent conditions within the Project. To-date nearly 10% of project participants have a mental health record. Mental health data are therefore vital in ensuring that a complete and relevant medical history is available for all participants.

Patient Reported Outcome Measures (PROMS). In combination with other data, this dataset allows correlation of outcomes and pain related measures to genetic markers and interventions in some key diseases. More generally they have utility in non-hypothesis driven research, including research into electronic health records.

Mortality data are essential for performing survival analyses: this is crucial information for research in combination with other medical history. Cause of death information is vital in order to determine if mortality is related to the primary disease of a participant or to highlight unforeseen trends. Knowledge of participant death is also vital for the correct analysis of medical timeline data and for the management of participant cohorts.

Demographic Data: These identifiable data sets are vital for the safe and efficient management of the participant cohort. They are used to ensure that Genomics' data applications are correct, do not cover duplicate participants, that withdrawn participants are excluded from data collection, and that participants’ details are accurate.

Genomics England works with industry through its Discovery Forum. The Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape. Industry partners comprise pharmaceutical, biotech and diagnostic companies, and those specialising in laboratory and data analysis. These companies have joined the Forum to work in a pre-competitive environment with access to a selection of genomic and associated clinical data. Ultimately, the Discovery Forum aims to help the 100,000 Genomes Project and its partners to turn research findings into treatments, diagnostics and benefits for patients as soon as possible. There are currently over 100 members of the Forum.

As the Discovery Forum is a collaborative venture, no fees are levied on participating organisations. All members of the Forum are obliged to publish all findings and research at the point at which intellectual property for any product is protected. Participants in the 100,000 Genomes Project have been asked explicitly to give consent for commercial companies to access their pseudonymised genome and health data.

The Forum was created in July 2017 and allows industrial partners to report back to Genomics England on what aspects of the data are proving to be most useful to their research studies, what data is missing and how the data should be collected and developed further so it is captures what industry needs, in a format that is compatible with their research and data systems. These partners act as a ‘critical friend’ and have made many helpful suggestions to increase the likelihood of successful research in the future for all those using Genomics England’s landmark data set.

The lawful basis for processing participant data under the General Data Protection Regulation (GDPR) used by Genomics England is Legitimate Interests as set out under Article 6(1)(f) of the GDPR. It is necessary for Genomics England to process Participant Data for its legitimate interests in carrying out medical research and in providing reports used by clinicians in their care of participants.

The processing is necessary to support and enable Genomics England's legitimate interests in enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancers.

The processing is necessary to support and enable Genomics England’s legitimate interests in:

· Creating a new genomic medicine service for the NHS (not a part of this agreement - will be part of a future amendment)

· Enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancer.

Patients and participants will be at the heart of this programme and include the participant panel, a 30 strong panel involved in Genomics England research committees.

The beneficiaries are:

· Participants through the work we do will influence their care;

· researchers and industry by giving them access to a unique ground-breaking resource of genomic data combined with life-course clinical data;

· and the wider public by accelerating the uptake of genomic medicine making it available to patients in the UK.

This Agreement also covers the use of the data for other purposes by Genomics England, subject to a valid Data Sharing Agreement being in place. The data held under this Agreement must not be used for other purposes until this has been agreed by NHS Digital under another Data Sharing Agreement.

Specific outputs for Genomics England are to continue to release updated genomic and clinical data into the TRE to support this ongoing research. Each research group who accesses this data will have their own defined output strategy and expectations which they will aim to deliver against. A full list of scientific publications and conferences/posters can be found on the Genomics England website. Recent specific examples of journal outputs are as follows:

- A systematic analysis of splicing variants identifies new diagnoses in the 100,000 Genomes Project. Alexander J.M. Blakes, Htoo Wai, Ian Davies, et al. Genome Medicine Jul 2022 DOI: 10.1186/s13073-022-01087-x. This demonstrated the clinical value of examining non-canonical splicing variants in individuals with unsolved rare diseases by identifying 35 new likely diagnoses from 258 probands with an unsolved rare disease.

- Prognosis and oncogenomic profiling of patients with tropomyosin receptor kinase fusion cancer in the 100,000 genomes project. John Bridgewater, Xiaolong Jiao, Mounika Parimi, et al. Cancer Treatment and Research Communications Aug 2022 DOI: 10.1016/j.ctarc.2022.100623. This study supports the hypothesis that Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are primary oncogenic drivers and the co-occurrence of NTRK gene fusions with other oncogenic alterations is rare. Overall survival was not statistically significant between NTRK and non-NTRK tumour patients.

- Participant experiences of genome sequencing for rare diseases in the 100,000 Genomes Project: a mixed methods study. Michelle Peter, Jennifer Hammond, Saskia C. Sanderson, et al. European Journal of Human Genetics Mar 2022 DOI: https://doi.org/10.1038/s41431-022-01065-2. This study highlights how expectation-setting is critical when offering genome sequencing, and that post-test counselling is important regardless of the GS result received, with parents perhaps needing additional emotional support.

• Patient benefit: providing clinical diagnosis and in time, new or more effective treatments for NHS patients. The project found that using WGS led to a new diagnosis for 25% of the participants. Of these new diagnoses, 14% found variations in regions of the genome that would be missed by other methods, including other types of non-whole genomic tests.

• New scientific insights and discovery: with the consent of patients, creating a database of 100,000 whole genome sequences linked to continually updated long term patient health and personal information for analysis by researchers. This has enhanced genomic healthcare research by creating the largest genomic healthcare data resource in the world, which in turn will uncover answers for participants both now and in the future through genomic-level analysis of conditions.

• Accelerating the uptake of genomic medicine in the NHS: working with NHSE and other partners to deliver a scale-able WGS and informatics platform to enable these services to be made widely available for NHS patients. In addition, through the Genomics England Clinical Interpretation Partnership (GeCIP), creating a mechanism to both continually improve the accuracy and reliability of information fed back to patients and add to knowledge of the genetic basis of disease. This acceleration significantly contributed to delivering the Genomics Medicine Service (GMS) for the NHS, which makes whole genome sequencing part of routine healthcare.

• Stimulating and enhancing UK industry and investment: by providing access to this unique data resource by industry for the purpose of developing new knowledge, methods of analysis, medicines, diagnostics and devices. The creation of the Discovery Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape.

• Increasing public knowledge and support for genomic medicine: delivering an ethical and transparent programme which has public trust and confidence and working with a range of partners to increase knowledge of genomics. After involving participants in all stages of the pioneering 100,000 Genomes Project and putting a trusted system in place contributed to a major dialogue led by Ipsos MORI and commissioned by Genomics England and co-funded by UK Research and Innovation’s Sciencewise programme in 2019 (post 100,000 genomes project completion) found the public are enthusiastic and optimistic about the potential for genomic medicine.

A genome is the body’s instruction manual - a copy is stored in almost every healthy cell in your body. The study of that genome and all the technologies needed to analyse and interpret it is called genomics.

Genomics England was established by the Department of Health to deliver the 100,000 Genomes Project. This followed the announcement in December 2012 by the Prime Minister of a programme of whole genome sequencing (WGS) as part of the UK Government’s Life Sciences Strategy. The principal objective of the 100,000 Genomes Project was to sequence 100,000 genomes from participants with cancer and rare disorders, and to link the sequence data to a standardised, extensible account of diagnosis, treatment, and outcomes gathered at recruitment, but primarily through the ongoing collection of medical records.

Combining genomic sequence data with medical records has created a ground-breaking research resource. Researchers are currently studying how best to use genomics in healthcare and how best to interpret the data to help patients. The causes, diagnosis and treatment of disease is also being investigated. Revealing which variants cause disease is also helping companies find new targeted medicines. Kick-starting a UK genomics industry was another key aim of the project and the UK now has a vibrant genomics ecosystem.

The project was designed to create a new genomic medicine service for the NHS. It was also designed to create new capability for the clinical genomics research, both academic and industrial, through the creation of a unique medical data set combining genomic sequence data with medical records within a secure research infrastructure.

Genomics England has sought to obtain information from participants’ medical records that span their entire lifetime. The DNA sequence, and information from patients’ health records and provided by the participants, are collected and stored securely as a resource for use by approved researchers for scientific and medical purposes during the life, and after the death, of participants. Diagnoses arising from the sequencing and analysis of the participants’ DNA are being fed back to participants: for many they are receiving a diagnosis for the first time.

The way in which the NHS is able to link a whole lifetime of medical records with a person’s genome data and the fact it can do this on a large scale is unique. The richness of this data can help to understand disease and to tease apart the complex relationship between our genes, what happens to us in our lives and illness.

The richness of the high-quality data sets is crucial to the success of the 100,000 Genomes Project in delivering value to the NHS. The evaluation of WGS data in the context of rich and extended phenotypes derived from electronic health records adds significant value. The richness of the Project dataset allows Genomics England to move beyond the primary phenotype that led to the patient’s enrolment to evaluate the genome sequence in the context of other continuous traits, diseases and responses to therapy.

The 100,000 Genomes Project has completed recruitment of rare disease participants and cancer patients in early 2019.

Genomics England will now continue to gather and provide genomic and clinical data for this cohort to continue the diagnostic and research aims of the project.

To achieve these goals Genomics wish to continue to collect the following datasets:

Hospital Episode Statistics: Outpatients, Admitted Patient Care, Critical Care and Accident & Emergency. These datasets provide the core clinical data for participants and are vital to the provision of a detailed medical history for participants.

Diagnostic Imaging Dataset. This provides invaluable, detailed information to build on participants’ phenotypes, e.g. tumour size and spread in cancer, adding to the understanding of patients’ histories on individual and cohort level and their relationship with genomic alterations.

Mental Health Data sets: Minimum Data Set, Mental Health and Learning Disabilities Data Set, and Mental Health Services Data Set. The 100,000 Genomes Project includes recruitment of psychiatric diseases and others with mental health phenotypes: intellectual disability and seizures are some of the most prevalent conditions within the Project. To-date nearly 10% of project participants have a mental health record. Mental health data are therefore vital in ensuring that a complete and relevant medical history is available for all participants.

Patient Reported Outcome Measures (PROMS). In combination with other data, this dataset allows correlation of outcomes and pain related measures to genetic markers and interventions in some key diseases. More generally they have utility in non-hypothesis driven research, including research into electronic health records.

Mortality data are essential for performing survival analyses: this is crucial information for research in combination with other medical history. Cause of death information is vital in order to determine if mortality is related to the primary disease of a participant or to highlight unforeseen trends. Knowledge of participant death is also vital for the correct analysis of medical timeline data and for the management of participant cohorts.

Demographic Data: These identifiable data sets are vital for the safe and efficient management of the participant cohort. They are used to ensure that Genomics' data applications are correct, do not cover duplicate participants, that withdrawn participants are excluded from data collection, and that participants’ details are accurate.

Genomics England works with industry through its Discovery Forum. The Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape. Industry partners comprise pharmaceutical, biotech and diagnostic companies, and those specialising in laboratory and data analysis. These companies have joined the Forum to work in a pre-competitive environment with access to a selection of genomic and associated clinical data. Ultimately, the Discovery Forum aims to help the 100,000 Genomes Project and its partners to turn research findings into treatments, diagnostics and benefits for patients as soon as possible. There are currently over 100 members of the Forum.

As the Discovery Forum is a collaborative venture, no fees are levied on participating organisations. All members of the Forum are obliged to publish all findings and research at the point at which intellectual property for any product is protected. Participants in the 100,000 Genomes Project have been asked explicitly to give consent for commercial companies to access their pseudonymised genome and health data.

The Forum was created in July 2017 and allows industrial partners to report back to Genomics England on what aspects of the data are proving to be most useful to their research studies, what data is missing and how the data should be collected and developed further so it is captures what industry needs, in a format that is compatible with their research and data systems. These partners act as a ‘critical friend’ and have made many helpful suggestions to increase the likelihood of successful research in the future for all those using Genomics England’s landmark data set.

The lawful basis for processing participant data under the General Data Protection Regulation (GDPR) used by Genomics England is Legitimate Interests as set out under Article 6(1)(f) of the GDPR. It is necessary for Genomics England to process Participant Data for its legitimate interests in carrying out medical research and in providing reports used by clinicians in their care of participants.

The processing is necessary to support and enable Genomics England's legitimate interests in enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancers.

The processing is necessary to support and enable Genomics England’s legitimate interests in:

· Creating a new genomic medicine service for the NHS (not a part of this agreement - will be part of a future amendment)

· Enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancer.

Patients and participants will be at the heart of this programme and include the participant panel, a 30 strong panel involved in Genomics England research committees.

The beneficiaries are:

· Participants through the work we do will influence their care;

· researchers and industry by giving them access to a unique ground-breaking resource of genomic data combined with life-course clinical data;

· and the wider public by accelerating the uptake of genomic medicine making it available to patients in the UK.

To confirm - this agreement does not cover (at present) the use of data for the Genomic Medicine Service (GMS). Genomics England will submit an amendment with relevant documentation so that the use of NHS Digital data can be approved for the GMS.

The project was established to sequence 100,000 genomes from around 85,000 NHS patients affected by a rare disease, or cancer.

The Project would also create a new genomic medicine service for the NHS – transforming the way people are cared for and bringing advanced diagnosis and personalised treatments to all those who need them.

Combining genomic sequence data with medical records has created a ground-breaking research resource. Researchers are currently studying how best to use genomics in healthcare and how best to interpret the data to help patients. The causes, diagnosis and treatment of disease is also being investigated. Revealing which variants cause disease is also helping companies find new targeted medicines. Kick-starting a UK genomics industry was another key aim of the project and the UK now has a vibrant genomics ecosystem.

Recruitment of participants to the 100,000 Genomes Project was completed in 2018, with the 100,000th sequence achieved in December 2018. Genomics England is committed to continue gathering life-long clinical data from the participants and making these available in the Trusted Research Environment (TRE).

Specific outputs over the period of this agreement are therefore to release updated genomic and clinical data for the 100,000 genomes participants into the TRE on the dates shown above.

• Patient benefit: providing clinical diagnosis and in time, new or more effective treatments for NHS patients. The project found that using WGS led to a new diagnosis for 25% of the participants. Of these new diagnoses, 14% found variations in regions of the genome that would be missed by other methods, including other types of non-whole genomic tests.

• New scientific insights and discovery: with the consent of patients, creating a database of 100,000 whole genome sequences linked to continually updated long term patient health and personal information for analysis by researchers. This has enhanced genomic healthcare research by creating the largest genomic healthcare data resource in the world, which in turn will uncover answers for participants both now and in the future through genomic-level analysis of conditions.

• Accelerating the uptake of genomic medicine in the NHS: working with NHSE and other partners to deliver a scale-able WGS and informatics platform to enable these services to be made widely available for NHS patients. In addition, through the Genomics England Clinical Interpretation Partnership (GeCIP), creating a mechanism to both continually improve the accuracy and reliability of information fed back to patients and add to knowledge of the genetic basis of disease. This acceleration significantly contributed to delivering the Genomics Medicine Service (GMS) for the NHS, which makes whole genome sequencing part of routine healthcare.

• Stimulating and enhancing UK industry and investment: by providing access to this unique data resource by industry for the purpose of developing new knowledge, methods of analysis, medicines, diagnostics and devices. The creation of the Discovery Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape.

• Increasing public knowledge and support for genomic medicine: delivering an ethical and transparent programme which has public trust and confidence and working with a range of partners to increase knowledge of genomics. After involving participants in all stages of the pioneering 100,000 Genomes Project and putting a trusted system in place contributed to a major dialogue led by Ipsos MORI and commissioned by Genomics England and co-funded by UK Research and Innovation’s Sciencewise programme in 2019 (post 100,000 genomes project completion) found the public are enthusiastic and optimistic about the potential for genomic medicine.

A genome is the body’s instruction manual - a copy is stored in almost every healthy cell in your body. The study of that genome and all the technologies needed to analyse and interpret it is called genomics.

Genomics England was established by the Department of Health to deliver the 100,000 Genomes Project. This followed the announcement in December 2012 by the Prime Minister of a programme of whole genome sequencing (WGS) as part of the UK Government’s Life Sciences Strategy. The principal objective of the 100,000 Genomes Project was to sequence 100,000 genomes from participants with cancer and rare disorders, and to link the sequence data to a standardised, extensible account of diagnosis, treatment, and outcomes gathered at recruitment, but primarily through the ongoing collection of medical records.

Combining genomic sequence data with medical records has created a ground-breaking research resource. Researchers are currently studying how best to use genomics in healthcare and how best to interpret the data to help patients. The causes, diagnosis and treatment of disease is also being investigated. Revealing which variants cause disease is also helping companies find new targeted medicines. Kick-starting a UK genomics industry was another key aim of the project and the UK now has a vibrant genomics ecosystem.

The project was designed to create a new genomic medicine service for the NHS. It was also designed to create new capability for the clinical genomics research, both academic and industrial, through the creation of a unique medical data set combining genomic sequence data with medical records within a secure research infrastructure.

Genomics England has sought to obtain information from participants’ medical records that span their entire lifetime. The DNA sequence, and information from patients’ health records and provided by the participants, are collected and stored securely as a resource for use by approved researchers for scientific and medical purposes during the life, and after the death, of participants. Diagnoses arising from the sequencing and analysis of the participants’ DNA are being fed back to participants: for many they are receiving a diagnosis for the first time.

The way in which the NHS is able to link a whole lifetime of medical records with a person’s genome data and the fact it can do this on a large scale is unique. The richness of this data can help to understand disease and to tease apart the complex relationship between our genes, what happens to us in our lives and illness.

The richness of the high-quality data sets is crucial to the success of the 100,000 Genomes Project in delivering value to the NHS. The evaluation of WGS data in the context of rich and extended phenotypes derived from electronic health records adds significant value. The richness of the Project dataset allows Genomics England to move beyond the primary phenotype that led to the patient’s enrolment to evaluate the genome sequence in the context of other continuous traits, diseases and responses to therapy.

The 100,000 Genomes Project has completed recruitment of rare disease participants and cancer patients in early 2019.

Genomics England will now continue to gather and provide genomic and clinical data for this cohort to continue the diagnostic and research aims of the project.

To achieve these goals Genomics wish to continue to collect the following datasets:

Hospital Episode Statistics: Outpatients, Admitted Patient Care, Critical Care and Accident & Emergency. These datasets provide the core clinical data for participants and are vital to the provision of a detailed medical history for participants.

Diagnostic Imaging Dataset. This provides invaluable, detailed information to build on participants’ phenotypes, e.g. tumour size and spread in cancer, adding to the understanding of patients’ histories on individual and cohort level and their relationship with genomic alterations.

Mental Health Data sets: Minimum Data Set, Mental Health and Learning Disabilities Data Set, and Mental Health Services Data Set. The 100,000 Genomes Project includes recruitment of psychiatric diseases and others with mental health phenotypes: intellectual disability and seizures are some of the most prevalent conditions within the Project. To-date nearly 10% of project participants have a mental health record. Mental health data are therefore vital in ensuring that a complete and relevant medical history is available for all participants.

Patient Reported Outcome Measures (PROMS). In combination with other data, this dataset allows correlation of outcomes and pain related measures to genetic markers and interventions in some key diseases. More generally they have utility in non-hypothesis driven research, including research into electronic health records.

Mortality data are essential for performing survival analyses: this is crucial information for research in combination with other medical history. Cause of death information is vital in order to determine if mortality is related to the primary disease of a participant or to highlight unforeseen trends. Knowledge of participant death is also vital for the correct analysis of medical timeline data and for the management of participant cohorts.

Demographic Data: These identifiable data sets are vital for the safe and efficient management of the participant cohort. They are used to ensure that Genomics' data applications are correct, do not cover duplicate participants, that withdrawn participants are excluded from data collection, and that participants’ details are accurate.

Genomics England works with industry through its Discovery Forum. The Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape. Industry partners comprise pharmaceutical, biotech and diagnostic companies, and those specialising in laboratory and data analysis. These companies have joined the Forum to work in a pre-competitive environment with access to a selection of genomic and associated clinical data. Ultimately, the Discovery Forum aims to help the 100,000 Genomes Project and its partners to turn research findings into treatments, diagnostics and benefits for patients as soon as possible. There are currently over 100 members of the Forum.

As the Discovery Forum is a collaborative venture, no fees are levied on participating organisations. All members of the Forum are obliged to publish all findings and research at the point at which intellectual property for any product is protected. Participants in the 100,000 Genomes Project have been asked explicitly to give consent for commercial companies to access their pseudonymised genome and health data.

The Forum was created in July 2017 and allows industrial partners to report back to Genomics England on what aspects of the data are proving to be most useful to their research studies, what data is missing and how the data should be collected and developed further so it is captures what industry needs, in a format that is compatible with their research and data systems. These partners act as a ‘critical friend’ and have made many helpful suggestions to increase the likelihood of successful research in the future for all those using Genomics England’s landmark data set.

The lawful basis for processing participant data under the General Data Protection Regulation (GDPR) used by Genomics England is Legitimate Interests as set out under Article 6(1)(f) of the GDPR. It is necessary for Genomics England to process Participant Data for its legitimate interests in carrying out medical research and in providing reports used by clinicians in their care of participants.

The processing is necessary to support and enable Genomics England's legitimate interests in enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancers.

The processing is necessary to support and enable Genomics England’s legitimate interests in:

· Creating a new genomic medicine service for the NHS (not a part of this agreement - will be part of a future amendment)

· Enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancer.

Patients and participants will be at the heart of this programme and include the participant panel, a 30 strong panel involved in Genomics England research committees.

The beneficiaries are:

· Participants through the work we do will influence their care;

· researchers and industry by giving them access to a unique ground-breaking resource of genomic data combined with life-course clinical data;

· and the wider public by accelerating the uptake of genomic medicine making it available to patients in the UK.

To confirm - this agreement does not cover (at present) the use of data for the Genomic Medicine Service (GMS). Genomics England will submit an amendment with relevant documentation so that the use of NHS Digital data can be approved for the GMS.

The project was established to sequence 100,000 genomes from around 85,000 NHS patients affected by a rare disease, or cancer.

The Project would also create a new genomic medicine service for the NHS – transforming the way people are cared for and bringing advanced diagnosis and personalised treatments to all those who need them.

Combining genomic sequence data with medical records has created a ground-breaking research resource. Researchers are currently studying how best to use genomics in healthcare and how best to interpret the data to help patients. The causes, diagnosis and treatment of disease is also being investigated. Revealing which variants cause disease is also helping companies find new targeted medicines. Kick-starting a UK genomics industry was another key aim of the project and the UK now has a vibrant genomics ecosystem.

Recruitment of participants to the 100,000 Genomes Project was completed in 2018, with the 100,000th sequence achieved in December 2018. Genomics England is committed to continue gathering life-long clinical data from the participants and making these available in the Research Environment.

Specific outputs over the period of this agreement are therefore to release updated genomic and clinical data for the 100,000 genomes participants into the Research Environment on the dates shown above.

The clinical benefit the 100,000 project brought to the participants acted as evidence to support the NHS to commit to whole genome sequencing as a standard of care for rare disease and cancer clinical indications: https://www.england.nhs.uk/genomics/nhs-genomic-med-service/

The yielded research benefits are being published on the Genomics England website’s publication page: https://www.genomicsengland.co.uk/about-gecip/publications/ and conference research outputs page: https://www.genomicsengland.co.uk/about-gecip/publications/further-research-outputs/

Further Genomics England has built upon its commitment to lead on Government’s technology and innovation agenda by forging partnership with industry. The creation of the Discovery Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape. Industry partners have a variety of outcomes measures and not all focus on publication for confirmation. We do however invite industry partners to present their work at conferences and keep up-to-date with their progress through our Strategic partnership directors.

A genome is the body’s instruction manual - a copy is stored in almost every healthy cell in your body. The study of that genome and all the technologies needed to analyse and interpret it is called genomics.

Genomics England was established by the Department of Health to deliver the 100,000 Genomes Project. This followed the announcement in December 2012 by the Prime Minister of a programme of whole genome sequencing (WGS) as part of the UK Government’s Life Sciences Strategy. The principal objective of the 100,000 Genomes Project was to sequence 100,000 genomes from participants with cancer and rare disorders, and to link the sequence data to a standardised, extensible account of diagnosis, treatment, and outcomes gathered at recruitment, but primarily through the ongoing collection of medical records.

Combining genomic sequence data with medical records has created a ground-breaking research resource. Researchers are currently studying how best to use genomics in healthcare and how best to interpret the data to help patients. The causes, diagnosis and treatment of disease is also being investigated. Revealing which variants cause disease is also helping companies find new targeted medicines. Kick-starting a UK genomics industry was another key aim of the project and the UK now has a vibrant genomics ecosystem.

The project was designed to create a new genomic medicine service for the NHS. It was also designed to create new capability for the clinical genomics research, both academic and industrial, though the creation of a unique medical data set combining genomic sequence data with medical records within a secure research infrastructure.

Genomics England has sought to obtain information from participants’ medical records that span their entire lifetime. The DNA sequence, and information from patients’ health records and provided by the participants, are collected and stored securely as a resource for use by approved researchers for scientific and medical purposes during the life, and after the death, of participants. Diagnoses arising from the sequencing and analysis of the participants’ DNA are being fed back to Participants: for many they are receiving a diagnosis for the first time.

The way in which the NHS is able to link a whole lifetime of medical records with a person’s genome data and the fact it can do this on a large scale is unique. The richness of this data can help to understand disease and to tease apart the complex relationship between our genes, what happens to us in our lives and illness.

The richness of the high-quality data sets are crucial to the success of the 100,000 Genomes Project in delivering value to the NHS. The evaluation of whole genome sequencing (WGS) data in the context of rich and extended phenotypes derived from electronic health records adds significant value. The richness of the Project dataset allows Genomics England to move beyond the primary phenotype that led to the patient’s enrolment to evaluate the genome sequence in the context of other continuous traits, diseases and responses to therapy.

The 100,000 Genomes Project has completed recruitment of rare disease participants and cancer patients in early 2019.

Genomics England will now continue to gather and provide genomic and clinical data for this cohort to continue the diagnostic and research aims of the project.

To achieve these goals Genomics wish to continue to collect the following data-sets:

Hospital Episode Statistics: Outpatients, Admitted Patient Care, Critical Care and Accident & Emergency. These datasets provide the core clinical data for participants and are vital to the provision of a detailed medical history for participants.

Diagnostic Imaging Dataset. This provides invaluable, detailed information to build on participants’ phenotypes, e.g. tumour size and spread in cancer, adding to the understanding of patients’ histories on individual and cohort level and their relationship with genomic alterations.

Mental Health Data sets: Minimum Data Set, Mental Health and Learning Disabilities Data Set, and Mental Health Services Data Set. The 100,000 Genomes Project includes recruitment of psychiatric diseases and others with mental health phenotypes: intellectual disability and seizures are some of the most prevalent conditions within the Project. To-date nearly 10% of project participants have a mental health record. Mental health data are therefore vital in ensuring that a complete and relevant medical history is available for all participants.

Patient Reported Outcome Measures (PROMS). In combination with other data, this dataset allows correlation of outcomes and pain related measures to genetic markers and interventions in some key diseases. More generally they have utility in non-hypothesis driven research, including research into electronic health records.

Mortality data are essential for performing survival analyses: this is crucial information for research in combination with other medical history. Cause of death information is vital in order to determine if mortality is related to the primary disease of a participant or to highlight unforeseen trends. Knowledge of participant death is also vital for the correct analysis of medical timeline data and for the management of participant cohorts.

Demographic Data: These identifiable data sets are vital for the safe and efficient management of the participant cohort. They are used to ensure that our data applications are correct and do not cover duplicate participants, that withdrawn participants are excluded from data collection, and that participants’ details are accurate.

Genomics England works with industry through its Discovery Forum. The Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape. Industry partners comprise pharmaceutical, biotech and diagnostic companies, and those specialising in laboratory and data analysis. These companies have joined the Forum to work in a pre-competitive environment with access to a selection of genomic and associated clinical data. Ultimately, the Discovery Forum aims to help the 100,000 Genomes Project and its partners to turn research findings into treatments, diagnostics and benefits for patients as soon as possible. There are currently over 100 members of the Forum.

As the Discovery Forum is a collaborative venture, no fees are levied on participating organisations. All members of the Forum are obliged to publish all findings and research at the point at which intellectual property for any product is protected. Participants in the 100,000 Genomes Project have been asked explicitly to give consent for commercial companies to access their de-identified genome and health data.

The Forum was created in July 2017 and allows industrial partners to report back to Genomics England on what aspects of the data are proving to be most useful to their research studies, what data is missing and how the data should be collected and developed further so it is captures what industry needs, in a format that is compatible with their research and data systems. These partners act as a ‘critical friend’ and have made many helpful suggestions to increase the likelihood of successful research in the future for all those using Genomics England’s landmark data set.

The lawful basis for processing Participant Data under the General Data Protection Regulation (GDPR) used by Genomics England is Legitimate Interests as set out under Article 6(1)(f) of the GDPR. It is necessary for Genomics England to process Participant Data for its legitimate interests in carrying out medical research and in providing reports used by clinicians in their care of Participants.

The processing is necessary to support and enable Genomics England's legitimate interests in enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancers.

The processing is necessary to support and enable Genomics England’s legitimate interests in:

· Creating a new genomic medicine service for the NHS (not a part of this agreement - will be part of a future amendment)

· Enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancer.

The beneficiaries are:

· Participants through the work we do will influence their care;

· researchers and industry by giving them access to a unique ground-breaking resource of genomic data combined with life-course clinical data;

· and the wider public by accelerating the uptake of genomic medicine making it available to patients in the UK.

Patients and participants will be at the heart of this programme and include the participant panel, a 30 strong panel involved in Genomics England research committees.

The beneficiaries are:

o Participants - through the work Genomics England do will ultimately influence their care;

o researchers and industry - by giving them access to a unique ground-breaking resource of genomic data combined with life-course clinical data;

o and the wider public - by accelerating the uptake of genomic medicine making it available to patients in the UK.

To confirm - this agreement does not cover (at present) the use of data for the Genomic Medicine Service. Genomics England will submit an amendment with relevant documentation so that the use of NHS Digital data can be approved for the GMS.

Genomics England’s target was to complete sequencing of 100,000 genomes by the end of 2018 – this was achieved by December 2018 - - https://www.newscientist.com/article/2187499-uk-dna-project-hits-major-milestone-with-100000-genomes-sequenced/

By April 2017 over 41,000 whole genomes had been sequenced and, with the aid of clinical data, the first diagnoses were announced:

• First diagnoses from the pilot phase https://www.genomicsengland.co.uk/first-patients-diagnosed-through-the-100000-genomes-project/

• First children diagnosed through the project https://www.genomicsengland.co.uk/first-children-recieve-diagnoses-through-100000-genomes-project/

• Financial Times article: https://www.ft.com/content/d2e21cea-d684-11e6-944b-e7eb37a6aa8e

By November 2018 109,611 samples had been collected, 91,100 genomes sequenced and 37,591 results returned to referring NHS Genomic Medicine Centres. Recruitment to the 100,000 genomes project is now completed, but analysis and return of results will continue throughout the period of this agreement.

By May 2018 the Genomics England Research Environment was established to allow research access to de-identified genome and clinical data received from NHS Digital. Thirty disease and cross-cutting GeCIP research domains were requested and approved, with over 1,300 GeCIP members given access to the Research Environment. Genomics England had also created the industry Discovery Forum to provide a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape.

By the end of October 2018 the fifth quarterly release of new data into the Genomics England Research Environment was achieved. This release included 71,860 genomes and primary clinical data for 85,070 participants. It also included de-identified clinical data received from NHS Digital for 60,110 participants, totalling 4.2m records. 1,821 GeCIP members from 387 institutions and 33 research domains now requested and been given access to the Research Environment, and 70 research projects have been approved. Alongside this there are 89 members of the industry Discovery Forum, including 10 full members.

Genomics England plans further releases of genomic and clinical data, including clinical data received from NHS Digital, into the Research Environment on the following dates, in order to continue support for, and to further develop, this ground-breaking resource:

• 20th Aug 2020

• 20th Oct 2020

• 20th Dec 2020

Although the 100,000 genomes project has completed recruitment, Genomics England is committed to continue gathering life-long clinical data from the participants and making these available in the Research Environment.

Specific outputs over the period of this agreement are therefore to release updated genomic and clinical data for the 100,000 genomes participants into the Research Environment on the dates shown above.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide. (if using HES data)

December 2017:

Over 41,000 Genomes were sequenced as of December 2017. Participant stories can be found at: https://www.genomicsengland.co.uk/alexs-story/

Genomics England has built upon its commitment to lead on Governments technology and innovation agenda by forging partnership with industry. Examples of this included a new industry collaboration with leading life sciences companies Inivata and Thermo Fisher Scientific to improve understanding of cancer.

Public Health England has announced that Whole Genome Sequencing (WGS) is now being used to identify different strains of tuberculosis (TB). This is the first time that WGS has been used as a diagnostic solution for managing a disease on this scale anywhere in the world. The technique, developed in conjunction with the University of Oxford, allows faster and more accurate diagnoses, meaning patients can be treated with precisely the right medication more quickly.

Genomics England has now engaged devolved nations and is recruiting participants from Scotland and Wales.

May 2018:

Over 60,000 genomes have been sequenced and over 12,000 clinical reports have been issued to referring NHS Genomic Medicine Centres. Thirty disease and cross-cutting research domains have had their plans approved and now have access to 100,000 the Genomes Project Research Environment. The number of users with access to the Genomics England Research Environment is now over 1,300.

Twelve publications have arisen from or refer to the 100,000 Genomes Project during the last year, including:

• The 100,000 Genomes Project: bringing whole genome sequencing to the NHS. Clare Turnbull et al. BMJ 2018; doi: https://doi.org/10.1136/bmj.k1687 (24 April 2018)

• Identification of rare sequence variation underlying heritable pulmonary arterial hypertension. Nicholas W. Morrell et al. Nature Communications 2018;9; doi:10.1038/s41467-018-03672-4 (12 April 2018)

• Introducing genomics into cancer care. Sue Hill BRJ Surg 2018;105(2):e14-e15 (17 January 2018)

• Missense variants in the X-linked gene PRPS1 cause retinal degeneration in females. Alessia Fiorentino, Kaoru Fujinami, Gavin Arno et al. Hum Mutat 2017; doi:10.1002/humu.23349 (17 October 2017)

See https://www.genomicsengland.co.uk/category/updates/ and https://www.genomicsengland.co.uk/aboutgecip/ publications/ for details of news and publications.

Genomics England created the Discovery Forum in July 2017. It provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape.

November 2018:

Over 109,000 samples have now been collected, 91,100 genomes sequenced and 37,591 clinical reports issued to referring NHS Genomic Medicine Centres. 71,860 genomes have been made available in the Genomics Engalnd Research Environment.

1,821 GeCIP members from 387 institutions and 33 research domains now have access to the research environment. There are now 89 members of the industry Discovery Forum, including 10 full members.

Latest publications include:

• Challenges in implementing genomic medicine: the 100,000 Genomes Project. Julian G. Barwell, Rory B.G. O’Sullivan, Laura K. Mansbridge, Joanna M. Lowry, Huw R. Dorkins. J Transl Genet Genom 2018;2:13; https://doi.org/10.20517/jtgg.2018.17 (11 Sep 2018)

• What will follow the first hundred thousand genomes in the NHS? Malcolm Grant & John Paul Maytum. Per Med 2018; doi:10.2217/pme-2018-0025 (20 June 2018)

• Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL. Jenny Klintman, Katerina Barmpouti, Samantha JL Knight et al. Br J Haematol 2018; doi:10.1111/bjh.15406 (29 May 2018)

February 2019:

• Clinical and genetic variability in children with partial albinism. Campbell P, Ellingford JM, Parry NRA, et al. Nature Scientific Reports doi: 10.1038/s41598-019-51768-8 (12/11/2019)

• Secondary C1q Deficiency in Activated PI3Kδ Syndrome Type 2 Ying Hong, Sira Nanthapisal, Ebun Omoyinmi, et al. Frontiers in Immunologydoi: 10.3389/fimmu.2019.02589 (11/11/2019)

• Defective tubulin detyrosination causes structural brain abnormalities with cognitive deficiency in humans and mice Pagnamenta, Alistair T; Heemeryck, Pierre; Hilary C Martin, et al. Human Molecular Genetics doi: 10.1093/hmg/ddz186 (31/07/2019)

• Germline selection shapes the landscape of human mitochondrial DNA Wei, Wei; Chinnery, Patrick; et al Science doi: 10.1126/science.aau6520 (01/04/2019)

• Validating Whole Genome Sequencing (WGS) for clinical use in AML & ALL S. Henderson, A. Sosinsky, A. Hamblin, et al. British Journal of Haematology doi: 10.1111/bjh.15854 (27/03/2019)

• Opportunities and Challenges for Molecular Understanding of Ciliopathies–The 100,000 Genomes Project Wheway, Gabrielle; Mitchison, Hannah H. Frontiers in Genetics doi: 10.3389/fgene.2019.00569 (11/03/2019)

Whole-genome sequencing of rare disease patients in a national healthcare system Ouwehand, Willem H bioRxiv – pre-publication doi: 10.1101/507244 (01/01/2019)

April 2020:

• Genomic loci susceptible to systematic sequencing bias in clinical whole genomes Timothy M. Freeman, Genomics England Research Consortium, Dennis Wang, and Jason Harris Genome Research doi: 10.1101/gr.255349.119 (11/03/2020)

• Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli Cayetano Pleguezuelos-Manzano, Jens Puschhof, Axel Rosendahl Huber, et al. Nature doi: 10.1038/s41586-020-2080-8 (27/02/2020)

• Expanding Clinical Presentations Due to Variations in THOC2 mRNA Nuclear Export Factor Raman Kumar, Elizabeth Palmer, Alison E. Gardner, et al. Frontiers in Molecular Neuroscience doi: 10.3389/fnmol.2020.00012 (11/02/2020)

• Human and mouse essentiality screens as a resource for disease gene discovery Pilar Cacheiro, Violeta Muñoz-Fuentes, Stephen A. Murray, et al. Nature Communications doi: 10.1038/s41467-020-14284-2 (31/01/2020)

• A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome Sara Cuvertino, Verity Hartill, Alice Colyer, et al. Genetics in Medicine doi: 10.1038/s41436-019-0743-3 (17/01/2020)

One of the main outputs of the project was to provide a diverse and unique clinical dataset alongside genomic data to ensure continued learning and development from the already accrued knowledge. Continued data acquisition will allow researchers to follow clinical progression of disease and cancers. The dataset in terms of participants is largely stable, with no significant further additions. However, by migrating the data to a cloud based system, this allows further integration of data in developing cohort and genomic browser systems, allowing more in-depth real-time analysis

The role of the 100,000 project was to gain an understanding of the rationale of whole genome sequencing for standard of care testing. The value of the 100,000 project now means that the NHS will provide whole genome sequencing as standard of care for the first time this year. The findings from the 100,000 project were fed back to clinicians to ensure a understanding of how to interpret genomic data and the subsequent translation of that into the concept of personalized medicine - as per the legitimate interests for Genomics England.

The patient participant panel for the 100,000 Genomes project have supported grant and award nominations for Genomics England - celebrating their patient engagement.

A genome is the body’s instruction manual - a copy is stored in almost every healthy cell in your body. The study of that genome and all the technologies needed to analyse and interpret it is called genomics.

Genomics England was established by the Department of Health to deliver the 100,000 Genomes Project. This followed the announcement in December 2012 by the Prime Minister of a programme of whole genome sequencing (WGS) as part of the UK Government’s Life Sciences Strategy. The principal objective of the 100,000 Genomes Project was to sequence 100,000 genomes from participants with cancer and rare disorders, and to link the sequence data to a standardised, extensible account of diagnosis, treatment, and outcomes gathered at recruitment, but primarily through the ongoing collection of medical records.

Combining genomic sequence data with medical records has created a ground-breaking research resource. Researchers are currently studying how best to use genomics in healthcare and how best to interpret the data to help patients. The causes, diagnosis and treatment of disease is also being investigated. Revealing which variants cause disease is also helping companies find new targeted medicines. Kick-starting a UK genomics industry was another key aim of the project and the UK now has a vibrant genomics ecosystem.

The project was designed to create a new genomic medicine service for the NHS. It was also designed to create new capability for the clinical genomics research, both academic and industrial, though the creation of a unique medical data set combining genomic sequence data with medical records within a secure research infrastructure.

Genomics England has sought to obtain information from participants’ medical records that span their entire lifetime. The DNA sequence, and information from patients’ health records and provided by the participants, are collected and stored securely as a resource for use by approved researchers for scientific and medical purposes during the life, and after the death, of participants. Diagnoses arising from the sequencing and analysis of the participants’ DNA are being fed back to Participants: for many they are receiving a diagnosis for the first time.

The way in which the NHS is able to link a whole lifetime of medical records with a person’s genome data and the fact it can do this on a large scale is unique. The richness of this data can help to understand disease and to tease apart the complex relationship between our genes, what happens to us in our lives and illness.

The richness of the high-quality data sets are crucial to the success of the 100,000 Genomes Project in delivering value to the NHS. The evaluation of whole genome sequencing (WGS) data in the context of rich and extended phenotypes derived from electronic health records adds significant value. The richness of the Project dataset allows Genomics England to move beyond the primary phenotype that led to the patient’s enrolment to evaluate the genome sequence in the context of other continuous traits, diseases and responses to therapy.

The 100,000 Genomes Project has completed recruitment of rare disease participants and cancer patients in early 2019.

Genomics England will now continue to gather and provide genomic and clinical data for this cohort to continue the diagnostic and research aims of the project.

To achieve these goals Genomics wish to continue to collect the following data-sets:

Hospital Episode Statistics: Outpatients, Admitted Patient Care, Critical Care and Accident & Emergency. These datasets provide the core clinical data for participants and are vital to the provision of a detailed medical history for participants.

Diagnostic Imaging Dataset. This provides invaluable, detailed information to build on participants’ phenotypes, e.g. tumour size and spread in cancer, adding to the understanding of patients’ histories on individual and cohort level and their relationship with genomic alterations.

Mental Health Data sets: Minimum Data Set, Mental Health and Learning Disabilities Data Set, and Mental Health Services Data Set. The 100,000 Genomes Project includes recruitment of psychiatric diseases and others with mental health phenotypes: intellectual disability and seizures are some of the most prevalent conditions within the Project. To-date nearly 10% of project participants have a mental health record. Mental health data are therefore vital in ensuring that a complete and relevant medical history is available for all participants.

Patient Reported Outcome Measures (PROMS). In combination with other data, this dataset allows correlation of outcomes and pain related measures to genetic markers and interventions in some key diseases. More generally they have utility in non-hypothesis driven research, including research into electronic health records.

Mortality data are essential for performing survival analyses: this is crucial information for research in combination with other medical history. Cause of death information is vital in order to determine if mortality is related to the primary disease of a participant or to highlight unforeseen trends. Knowledge of participant death is also vital for the correct analysis of medical timeline data and for the management of participant cohorts.

Demographic Data: These identifiable data sets are vital for the safe and efficient management of the participant cohort. They are used to ensure that our data applications are correct and do not cover duplicate participants, that withdrawn participants are excluded from data collection, and that participants’ details are accurate.

Genomics England works with industry through its Discovery Forum. The Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape. Industry partners comprise pharmaceutical, biotech and diagnostic companies, and those specialising in laboratory and data analysis. These companies have joined the Forum to work in a pre-competitive environment with access to a selection of genomic and associated clinical data. Ultimately, the Discovery Forum aims to help the 100,000 Genomes Project and its partners to turn research findings into treatments, diagnostics and benefits for patients as soon as possible. There are currently over 100 members of the Forum.

As the Discovery Forum is a collaborative venture, no fees are levied on participating organisations. All members of the Forum are obliged to publish all findings and research at the point at which intellectual property for any product is protected. Participants in the 100,000 Genomes Project have been asked explicitly to give consent for commercial companies to access their de-identified genome and health data.

The Forum was created in July 2017 and allows industrial partners to report back to Genomics England on what aspects of the data are proving to be most useful to their research studies, what data is missing and how the data should be collected and developed further so it is captures what industry needs, in a format that is compatible with their research and data systems. These partners act as a ‘critical friend’ and have made many helpful suggestions to increase the likelihood of successful research in the future for all those using Genomics England’s landmark data set.

The lawful basis for processing Participant Data under the General Data Protection Regulation (GDPR) used by Genomics England is Legitimate Interests as set out under Article 6(1)(f) of the GDPR. It is necessary for Genomics England to process Participant Data for its legitimate interests in carrying out medical research and in providing reports used by clinicians in their care of Participants.

The processing is necessary to support and enable Genomics England's legitimate interests in enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancers.

The processing is necessary to support and enable Genomics England’s legitimate interests in:

· Creating a new genomic medicine service for the NHS (not a part of this agreement - will be part of a future amendment)

· Enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancer.

The beneficiaries are:

· Participants through the work we do will influence their care;

· researchers and industry by giving them access to a unique ground-breaking resource of genomic data combined with life-course clinical data;

· and the wider public by accelerating the uptake of genomic medicine making it available to patients in the UK.

Patients and participants will be at the heart of this programme and include the participant panel, a 30 strong panel involved in Genomics England research committees.

The beneficiaries are:

o Participants - through the work Genomics England do will ultimately influence their care;

o researchers and industry - by giving them access to a unique ground-breaking resource of genomic data combined with life-course clinical data;

o and the wider public - by accelerating the uptake of genomic medicine making it available to patients in the UK.

To confirm - this agreement does not cover (at present) the use of data for the Genomic Medicine Service. Genomics England will submit an amendment with relevant documentation so that the use of NHS Digital data can be approved for the GMS.

Genomics England’s target was to complete sequencing of 100,000 genomes by the end of 2018 – this was achieved by December 2018 - - https://www.newscientist.com/article/2187499-uk-dna-project-hits-major-milestone-with-100000-genomes-sequenced/

By April 2017 over 41,000 whole genomes had been sequenced and, with the aid of clinical data, the first diagnoses were announced:

• First diagnoses from the pilot phase https://www.genomicsengland.co.uk/first-patients-diagnosed-through-the-100000-genomes-project/

• First children diagnosed through the project https://www.genomicsengland.co.uk/first-children-recieve-diagnoses-through-100000-genomes-project/

• Financial Times article: https://www.ft.com/content/d2e21cea-d684-11e6-944b-e7eb37a6aa8e

By November 2018 109,611 samples had been collected, 91,100 genomes sequenced and 37,591 results returned to referring NHS Genomic Medicine Centres. Recruitment to the 100,000 genomes project is now completed, but analysis and return of results will continue throughout the period of this agreement.

By May 2018 the Genomics England Research Environment was established to allow research access to de-identified genome and clinical data received from NHS Digital. Thirty disease and cross-cutting GeCIP research domains were requested and approved, with over 1,300 GeCIP members given access to the Research Environment. Genomics England had also created the industry Discovery Forum to provide a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape.

By the end of October 2018 the fifth quarterly release of new data into the Genomics England Research Environment was achieved. This release included 71,860 genomes and primary clinical data for 85,070 participants. It also included de-identified clinical data received from NHS Digital for 60,110 participants, totalling 4.2m records. 1,821 GeCIP members from 387 institutions and 33 research domains now requested and been given access to the Research Environment, and 70 research projects have been approved. Alongside this there are 89 members of the industry Discovery Forum, including 10 full members.

Genomics England plans further releases of genomic and clinical data, including clinical data received from NHS Digital, into the Research Environment on the following dates, in order to continue support for, and to further develop, this ground-breaking resource:

• 20th Aug 2020

• 20th Oct 2020

• 20th Dec 2020

Although the 100,000 genomes project has completed recruitment, Genomics England is committed to continue gathering life-long clinical data from the participants and making these available in the Research Environment.

Specific outputs over the period of this agreement are therefore to release updated genomic and clinical data for the 100,000 genomes participants into the Research Environment on the dates shown above.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide. (if using HES data)

December 2017:

Over 41,000 Genomes were sequenced as of December 2017. Participant stories can be found at: https://www.genomicsengland.co.uk/alexs-story/

Genomics England has built upon its commitment to lead on Governments technology and innovation agenda by forging partnership with industry. Examples of this included a new industry collaboration with leading life sciences companies Inivata and Thermo Fisher Scientific to improve understanding of cancer.

Public Health England has announced that Whole Genome Sequencing (WGS) is now being used to identify different strains of tuberculosis (TB). This is the first time that WGS has been used as a diagnostic solution for managing a disease on this scale anywhere in the world. The technique, developed in conjunction with the University of Oxford, allows faster and more accurate diagnoses, meaning patients can be treated with precisely the right medication more quickly.

Genomics England has now engaged devolved nations and is recruiting participants from Scotland and Wales.

May 2018:

Over 60,000 genomes have been sequenced and over 12,000 clinical reports have been issued to referring NHS Genomic Medicine Centres. Thirty disease and cross-cutting research domains have had their plans approved and now have access to 100,000 the Genomes Project Research Environment. The number of users with access to the Genomics England Research Environment is now over 1,300.

Twelve publications have arisen from or refer to the 100,000 Genomes Project during the last year, including:

• The 100,000 Genomes Project: bringing whole genome sequencing to the NHS. Clare Turnbull et al. BMJ 2018; doi: https://doi.org/10.1136/bmj.k1687 (24 April 2018)

• Identification of rare sequence variation underlying heritable pulmonary arterial hypertension. Nicholas W. Morrell et al. Nature Communications 2018;9; doi:10.1038/s41467-018-03672-4 (12 April 2018)

• Introducing genomics into cancer care. Sue Hill BRJ Surg 2018;105(2):e14-e15 (17 January 2018)

• Missense variants in the X-linked gene PRPS1 cause retinal degeneration in females. Alessia Fiorentino, Kaoru Fujinami, Gavin Arno et al. Hum Mutat 2017; doi:10.1002/humu.23349 (17 October 2017)

See https://www.genomicsengland.co.uk/category/updates/ and https://www.genomicsengland.co.uk/aboutgecip/ publications/ for details of news and publications.

Genomics England created the Discovery Forum in July 2017. It provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape.

November 2018:

Over 109,000 samples have now been collected, 91,100 genomes sequenced and 37,591 clinical reports issued to referring NHS Genomic Medicine Centres. 71,860 genomes have been made available in the Genomics Engalnd Research Environment.

1,821 GeCIP members from 387 institutions and 33 research domains now have access to the research environment. There are now 89 members of the industry Discovery Forum, including 10 full members.

Latest publications include:

• Challenges in implementing genomic medicine: the 100,000 Genomes Project. Julian G. Barwell, Rory B.G. O’Sullivan, Laura K. Mansbridge, Joanna M. Lowry, Huw R. Dorkins. J Transl Genet Genom 2018;2:13; https://doi.org/10.20517/jtgg.2018.17 (11 Sep 2018)

• What will follow the first hundred thousand genomes in the NHS? Malcolm Grant & John Paul Maytum. Per Med 2018; doi:10.2217/pme-2018-0025 (20 June 2018)

• Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL. Jenny Klintman, Katerina Barmpouti, Samantha JL Knight et al. Br J Haematol 2018; doi:10.1111/bjh.15406 (29 May 2018)

February 2019:

• Clinical and genetic variability in children with partial albinism. Campbell P, Ellingford JM, Parry NRA, et al. Nature Scientific Reports doi: 10.1038/s41598-019-51768-8 (12/11/2019)

• Secondary C1q Deficiency in Activated PI3Kδ Syndrome Type 2 Ying Hong, Sira Nanthapisal, Ebun Omoyinmi, et al. Frontiers in Immunologydoi: 10.3389/fimmu.2019.02589 (11/11/2019)

• Defective tubulin detyrosination causes structural brain abnormalities with cognitive deficiency in humans and mice Pagnamenta, Alistair T; Heemeryck, Pierre; Hilary C Martin, et al. Human Molecular Genetics doi: 10.1093/hmg/ddz186 (31/07/2019)

• Germline selection shapes the landscape of human mitochondrial DNA Wei, Wei; Chinnery, Patrick; et al Science doi: 10.1126/science.aau6520 (01/04/2019)

• Validating Whole Genome Sequencing (WGS) for clinical use in AML & ALL S. Henderson, A. Sosinsky, A. Hamblin, et al. British Journal of Haematology doi: 10.1111/bjh.15854 (27/03/2019)

• Opportunities and Challenges for Molecular Understanding of Ciliopathies–The 100,000 Genomes Project Wheway, Gabrielle; Mitchison, Hannah H. Frontiers in Genetics doi: 10.3389/fgene.2019.00569 (11/03/2019)

Whole-genome sequencing of rare disease patients in a national healthcare system Ouwehand, Willem H bioRxiv – pre-publication doi: 10.1101/507244 (01/01/2019)

April 2020:

• Genomic loci susceptible to systematic sequencing bias in clinical whole genomes Timothy M. Freeman, Genomics England Research Consortium, Dennis Wang, and Jason Harris Genome Research doi: 10.1101/gr.255349.119 (11/03/2020)

• Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli Cayetano Pleguezuelos-Manzano, Jens Puschhof, Axel Rosendahl Huber, et al. Nature doi: 10.1038/s41586-020-2080-8 (27/02/2020)

• Expanding Clinical Presentations Due to Variations in THOC2 mRNA Nuclear Export Factor Raman Kumar, Elizabeth Palmer, Alison E. Gardner, et al. Frontiers in Molecular Neuroscience doi: 10.3389/fnmol.2020.00012 (11/02/2020)

• Human and mouse essentiality screens as a resource for disease gene discovery Pilar Cacheiro, Violeta Muñoz-Fuentes, Stephen A. Murray, et al. Nature Communications doi: 10.1038/s41467-020-14284-2 (31/01/2020)

• A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome Sara Cuvertino, Verity Hartill, Alice Colyer, et al. Genetics in Medicine doi: 10.1038/s41436-019-0743-3 (17/01/2020)

One of the main outputs of the project was to provide a diverse and unique clinical dataset alongside genomic data to ensure continued learning and development from the already accrued knowledge. Continued data acquisition will allow researchers to follow clinical progression of disease and cancers. The dataset in terms of participants is largely stable, with no significant further additions. However, by migrating the data to a cloud based system, this allows further integration of data in developing cohort and genomic browser systems, allowing more in-depth real-time analysis

The role of the 100,000 project was to gain an understanding of the rationale of whole genome sequencing for standard of care testing. The value of the 100,000 project now means that the NHS will provide whole genome sequencing as standard of care for the first time this year. The findings from the 100,000 project were fed back to clinicians to ensure a understanding of how to interpret genomic data and the subsequent translation of that into the concept of personalized medicine - as per the legitimate interests for Genomics England.

The patient participant panel for the 100,000 Genomes project have supported grant and award nominations for Genomics England - celebrating their patient engagement.

Genomics England was established by the Department of Health to deliver the 100,000 Genomes Project. This followed the announcement in December 2012 by the Prime Minister of a programme of whole genome sequencing (WGS) as part of the UK Government’s Life Sciences Strategy. The principal objective of the 100,000 Genomes Project was to sequence 100,000 genomes from participants with cancer and rare disorders, and to link the sequence data to a standardised, extensible account of diagnosis, treatment, and outcomes gathered at recruitment, but primarily through the ongoing collection of medical records.

The project was designed to create a new genomic medicine service for the NHS. It was also designed to create new capability for the clinical genomics research, both academic and industrial, though the creation of a unique medical data set combining genomic sequence data with medical records within a secure research infrastructure.

Genomics England has sought to obtain information from participants’ medical records that span their entire lifetime. The DNA sequence, and information from patients’ health records and provided by the participants, are collected and stored securely as a resource for use by approved researchers for scientific and medical purposes during the life, and after the death, of participants. Diagnoses arising from the sequencing and analysis of the participants’ DNA are being fed back to Participants: for many they are receiving a diagnosis for the first time.

The richness of the high-quality data sets are crucial to the success of the 100,000 Genomes Project in delivering value to the NHS. The evaluation of whole genome sequencing (WGS) data in the context of rich and extended phenotypes derived from electronic health records adds significant value. The richness of the Project dataset allows Genomics England to move beyond the primary phenotype that led to the patient’s enrolment to evaluate the genome sequence in the context of other continuous traits, diseases and responses to therapy.

The 100,000 Genomes Project has completed recruitment of rare disease participants and will complete recruitment of cancer patients in early 2019. Genomics England will now continue to gather and provide genomic and clinical data for this cohort to continue the diagnostic and research aims of the project.

To achieve these goals Genomics wish to continue to collect the following data-sets:

Hospital Episode Statistics: Outpatients, Admitted Patient Care, Critical Care and Accident & Emergency. These datasets provide the core clinical data for participants and are vital to the provision of a detailed medical history for participants.

Diagnostic Imaging Dataset. This provides invaluable, detailed information to build on participants’ phenotypes, e.g. tumour size and spread in cancer, adding to the understanding of patients’ histories on individual and cohort level and their relationship with genomic alterations.

Mental Health Data sets: Minimum Data Set, Mental Health and Learning Disabilities Data Set, and Mental Health Services Data Set. The 100,000 Genomes Project includes recruitment of psychiatric diseases and others with mental health phenotypes: intellectual disability and seizures are some of the most prevalent conditions within the Project. To-date nearly 10% of project participants have a mental health record. Mental health data are therefore vital in ensuring that a complete and relevant medical history is available for all participants.

Patient Reported Outcome Measures (PROMS). In combination with other data, this dataset allows correlation of outcomes and pain related measures to genetic markers and interventions in some key diseases. More generally they have utility in non-hypothesis driven research, including research into electronic health records.

MRIS: Cohort Event Notification, Cause of Death. Mortality data are essential for performing survival analyses and as a metric for success of medical care: this is crucial information for research in combination with other medical history. Cause of death information is vital in order to determine if mortality is related to the primary disease of a participant or to highlight unforeseen trends. Knowledge of participant death is also vital for the correct analysis of medical timeline data and for the management of participant cohorts.

MRIS: Members and Posting, List Cleaning Report, Flagging Current Status. These identifiable data sets are vital for the safe and efficient management of the participant cohort. They are used to ensure that our data applications are correct and do not cover duplicate participants, that withdrawn participants are excluded from data collection, and that participants’ details are accurate.

Genomics England works with industry through its Discovery Forum. The Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape. Industry partners comprise pharmaceutical, biotech and diagnostic companies, and those specialising in laboratory and data analysis. These companies have joined the Forum to work in a pre-competitive environment with access to a selection of genomic and associated clinical data. Ultimately, the Discovery Forum aims to help the 100,000 Genomes Project and its partners to turn research findings into treatments, diagnostics and benefits for patients as soon as possible. There are currently over 100 members of the Forum.

As the Discovery Forum is a collaborative venture, no fees are levied on participating organisations. All members of the Forum are obliged to publish all findings and research at the point at which intellectual property for any product is protected. Participants in the 100,000 Genomes Project have been asked explicitly to give consent for commercial companies to access their de-identified genome and health data.

The Forum was created in July 2017 and allows industrial partners to report back to Genomics England on what aspects of the data are proving to be most useful to their research studies, what data is missing and how the data should be collected and developed further so it is captures what industry needs, in a format that is compatible with their research and data systems. These partners act as a ‘critical friend’ and have made many helpful suggestions to increase the likelihood of successful research in the future for all those using Genomics England’s landmark data set.

The lawful basis for processing Participant Data under the General Data Protection

Regulation (GDPR) used by Genomics England is legitimate interests as set out under Article 6(1)(f) of the GDPR. It is necessary for Genomics England to process Participant Data for its legitimate interests in carrying out medical research and in providing reports used by clinicians in their care of Participants.

It is necessary for Genomics England to process Participant Data for its legitimate interests in carrying out medical research and in providing reports used by clinicians in their care of Participants.

The processing is necessary to support and enable Genomics England’s legitimate interests in:

· Creating a new genomic medicine service for the NHS;

· Enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancer.

The beneficiaries are:

· Participants through the work we do will influence their care;

· researchers and industry by giving them access to a unique ground-breaking resource of genomic data combined with life-course clinical data;

· and the wider public by accelerating the uptake of genomic medicine making it available to patients in the UK.

Genomics England’s target was to complete sequencing of 100,000 genomes by the end of 2018 – this was achieved by December 2018 - - https://www.newscientist.com/article/2187499-uk-dna-project-hits-major-milestone-with-100000-genomes-sequenced/

By April 2017 over 41,000 whole genomes had been sequenced and, with the aid of clinical data, the first diagnoses were announced:

• First diagnoses from the pilot phase https://www.genomicsengland.co.uk/first-patients-diagnosed-through-the-100000-genomes-project/

• First children diagnosed through the project https://www.genomicsengland.co.uk/first-children-recieve-diagnoses-through-100000-genomes-project/

• Financial Times article: https://www.ft.com/content/d2e21cea-d684-11e6-944b-e7eb37a6aa8e

By November 2018 109,611 samples had been collected, 91,100 genomes sequenced and 37,591 results returned to referring NHS Genomic Medicine Centres. Recruitment to the 100,000 genomes project is now completed, but analysis and return of results will continue throughout the period of this agreement.

By May 2018 the Genomics England Research Environment was established to allow research access to de-identified genome and clinical data received from NHS Digital. Thirty disease and cross-cutting GeCIP research domains were requested and approved, with over 1,300 GeCIP members given access to the Research Environment. Genomics England had also created the industry Discovery Forum to provide a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape.

By the end of October 2018 the fifth quarterly release of new data into the Genomics England Research Environment was achieved. This release included 71,860 genomes and primary clinical data for 85,070 participants. It also included de-identified clinical data received from NHS Digital for 60,110 participants, totalling 4.2m records. 1,821 GeCIP members from 387 institutions and 33 research domains now requested and been given access to the Research Environment, and 70 research projects have been approved. Alongside this there are 89 members of the industry Discovery Forum, including 10 full members.

Genomics England plans further releases of genomic and clinical data, including clinical data received from NHS Digital, into the Research Environment on the following dates, in order to continue support for, and to further develop, this ground-breaking resource:

• 28th Feb 19

• 30th Apr 19

• 31st Jul 19

• 31st Oct 19

Although the 100,000 genomes project has completed recruitment, Genomics England is committed to continue gathering life-long clinical data from the participants and making these available in the Research Environment.

Specific outputs over the period of this agreement are therefore to release updated genomic and clinical data for the 100,000 genomes participants into the Research Environment on the dates shown above.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide. (if using HES data)

Update December 2017

Over 41,000 Genomes were sequenced as of December 2017. Participant stories can be found at: https://www.genomicsengland.co.uk/alexs-story/

Genomics England has built upon its commitment to lead on Governments technology and innovation agenda by forging partnership with industry. Examples of this include a new industry collaboration with leading life sciences companies Inivata and Thermo Fisher Scientific to improve understanding of cancer.

Public Health England has announced that Whole Genome Sequencing (WGS) is now being used to identify different strains of tuberculosis (TB). This is the first time that WGS has been used as a diagnostic solution for managing a disease on this scale anywhere in the world. The technique, developed in conjunction with the University of Oxford, allows faster and more accurate diagnoses, meaning patients can be treated with precisely the right medication more quickly.

Genomics England has now engaged devolved nations and is recruiting participants from Scotland and Wales.

Update May 2018

Over 60,000 genomes have been sequenced and over 12,000 clinical reports have been issued to referring NHS Genomic Medicine Centres. Thirty disease and cross-cutting research domains have had their plans approved and now have access to 100,000 the Genomes Project Research Environment. The number of users with access to the Genomics England Research Environment is now over 1,300.

Twelve publications have arisen from or refer to the 100,000 Genomes Project during the last year, including:

• The 100,000 Genomes Project: bringing whole genome sequencing to the NHS. Clare Turnbull et al. BMJ 2018; doi: https://doi.org/10.1136/bmj.k1687 (24 April 2018)

• Identification of rare sequence variation underlying heritable pulmonary arterial hypertension. Nicholas W. Morrell et al. Nature Communications 2018;9; doi:10.1038/s41467-018-03672-4 (12 April 2018)

• Introducing genomics into cancer care. Sue Hill BRJ Surg 2018;105(2):e14-e15 (17 January 2018)

• Missense variants in the X-linked gene PRPS1 cause retinal degeneration in females. Alessia Fiorentino, Kaoru Fujinami, Gavin Arno et al. Hum Mutat 2017; doi:10.1002/humu.23349 (17 October 2017)

See https://www.genomicsengland.co.uk/category/updates/ and https://www.genomicsengland.co.uk/aboutgecip/ publications/ for details of news and publications.

Genomics England created the Discovery Forum in July 2017. It provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape.

Update November 2018

Over 109,000 samples have now been collected, 91,100 genomes sequenced and 37,591 clinical reports issued to referring NHS Genomic Medicine Centres. 71,860 genomes have been made available in the Genomics Engalnd Research Environment.

1,821 GeCIP members from 387 institutions and 33 research domains now have access to the research environment. There are now 89 members of the industry Discovery Forum, including 10 full members.

Latest publications include:

• Challenges in implementing genomic medicine: the 100,000 Genomes Project. Julian G. Barwell, Rory B.G. O’Sullivan, Laura K. Mansbridge, Joanna M. Lowry, Huw R. Dorkins. J Transl Genet Genom 2018;2:13; https://doi.org/10.20517/jtgg.2018.17 (11 Sep 2018)

• What will follow the first hundred thousand genomes in the NHS? Malcolm Grant & John Paul Maytum. Per Med 2018; doi:10.2217/pme-2018-0025 (20 June 2018)

• Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL. Jenny Klintman, Katerina Barmpouti, Samantha JL Knight et al. Br J Haematol 2018; doi:10.1111/bjh.15406 (29 May 2018)

Update 2019

• Clinical and genetic variability in children with partial albinism. Campbell P, Ellingford JM, Parry NRA, et al. Nature Scientific Reports doi: 10.1038/s41598-019-51768-8 (12/11/2019)

• Secondary C1q Deficiency in Activated PI3Kδ Syndrome Type 2 Ying Hong, Sira Nanthapisal, Ebun Omoyinmi, et al. Frontiers in Immunologydoi: 10.3389/fimmu.2019.02589 (11/11/2019)

• Defective tubulin detyrosination causes structural brain abnormalities with cognitive deficiency in humans and mice Pagnamenta, Alistair T; Heemeryck, Pierre; Hilary C Martin, et al. Human Molecular Genetics doi: 10.1093/hmg/ddz186 (31/07/2019)

• Germline selection shapes the landscape of human mitochondrial DNA Wei, Wei; Chinnery, Patrick; et al Science doi: 10.1126/science.aau6520 (01/04/2019)

• Validating Whole Genome Sequencing (WGS) for clinical use in AML & ALL S. Henderson, A. Sosinsky, A. Hamblin, et al. British Journal of Haematology doi: 10.1111/bjh.15854 (27/03/2019)

• Opportunities and Challenges for Molecular Understanding of Ciliopathies–The 100,000 Genomes Project Wheway, Gabrielle; Mitchison, Hannah H. Frontiers in Genetics doi: 10.3389/fgene.2019.00569 (11/03/2019)

Whole-genome sequencing of rare disease patients in a national healthcare system Ouwehand, Willem H bioRxiv – pre-publication doi: 10.1101/507244 (01/01/2019)

Update Apr 2020

• Genomic loci susceptible to systematic sequencing bias in clinical whole genomes Timothy M. Freeman, Genomics England Research Consortium, Dennis Wang, and Jason Harris Genome Research doi: 10.1101/gr.255349.119 (11/03/2020)

• Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli Cayetano Pleguezuelos-Manzano, Jens Puschhof, Axel Rosendahl Huber, et al. Nature doi: 10.1038/s41586-020-2080-8 (27/02/2020)

• Expanding Clinical Presentations Due to Variations in THOC2 mRNA Nuclear Export Factor Raman Kumar, Elizabeth Palmer, Alison E. Gardner, et al. Frontiers in Molecular Neuroscience doi: 10.3389/fnmol.2020.00012 (11/02/2020)

• Human and mouse essentiality screens as a resource for disease gene discovery Pilar Cacheiro, Violeta Muñoz-Fuentes, Stephen A. Murray, et al. Nature Communications doi: 10.1038/s41467-020-14284-2 (31/01/2020)

• A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome Sara Cuvertino, Verity Hartill, Alice Colyer, et al. Genetics in Medicine doi: 10.1038/s41436-019-0743-3 (17/01/2020)

Genomics England was established by the Department of Health to deliver the 100,000 Genomes Project. This followed the announcement in December 2012 by the Prime Minister of a programme of whole genome sequencing (WGS) as part of the UK Government’s Life Sciences Strategy. The principal objective of the 100,000 Genomes Project was to sequence 100,000 genomes from participants with cancer and rare disorders, and to link the sequence data to a standardised, extensible account of diagnosis, treatment, and outcomes gathered at recruitment, but primarily through the ongoing collection of medical records.

The project was designed to create a new genomic medicine service for the NHS. It was also designed to create new capability for the clinical genomics research, both academic and industrial, though the creation of a unique medical data set combining genomic sequence data with medical records within a secure research infrastructure.

Genomics England has sought to obtain information from participants’ medical records that span their entire lifetime. The DNA sequence, and information from patients’ health records and provided by the participants, are collected and stored securely as a resource for use by approved researchers for scientific and medical purposes during the life, and after the death, of participants. Diagnoses arising from the sequencing and analysis of the participants’ DNA are being fed back to Participants: for many they are receiving a diagnosis for the first time.

The richness of the high-quality data sets are crucial to the success of the 100,000 Genomes Project in delivering value to the NHS. The evaluation of whole genome sequencing (WGS) data in the context of rich and extended phenotypes derived from electronic health records adds significant value. The richness of the Project dataset allows Genomics England to move beyond the primary phenotype that led to the patient’s enrolment to evaluate the genome sequence in the context of other continuous traits, diseases and responses to therapy.

The 100,000 Genomes Project has completed recruitment of rare disease participants and will complete recruitment of cancer patients in early 2019. Genomics England will now continue to gather and provide genomic and clinical data for this cohort to continue the diagnostic and research aims of the project.

To achieve these goals Genomics wish to continue to collect the following data-sets:

Hospital Episode Statistics: Outpatients, Admitted Patient Care, Critical Care and Accident & Emergency. These datasets provide the core clinical data for participants and are vital to the provision of a detailed medical history for participants.

Diagnostic Imaging Dataset. This provides invaluable, detailed information to build on participants’ phenotypes, e.g. tumour size and spread in cancer, adding to the understanding of patients’ histories on individual and cohort level and their relationship with genomic alterations.

Mental Health Data sets: Minimum Data Set, Mental Health and Learning Disabilities Data Set, and Mental Health Services Data Set. The 100,000 Genomes Project includes recruitment of psychiatric diseases and others with mental health phenotypes: intellectual disability and seizures are some of the most prevalent conditions within the Project. To-date nearly 10% of project participants have a mental health record. Mental health data are therefore vital in ensuring that a complete and relevant medical history is available for all participants.

Patient Reported Outcome Measures (PROMS). In combination with other data, this dataset allows correlation of outcomes and pain related measures to genetic markers and interventions in some key diseases. More generally they have utility in non-hypothesis driven research, including research into electronic health records.

MRIS: Cohort Event Notification, Cause of Death. Mortality data are essential for performing survival analyses and as a metric for success of medical care: this is crucial information for research in combination with other medical history. Cause of death information is vital in order to determine if mortality is related to the primary disease of a participant or to highlight unforeseen trends. Knowledge of participant death is also vital for the correct analysis of medical timeline data and for the management of participant cohorts.

MRIS: Members and Posting, List Cleaning Report, Flagging Current Status. These identifiable data sets are vital for the safe and efficient management of the participant cohort. They are used to ensure that our data applications are correct and do not cover duplicate participants, that withdrawn participants are excluded from data collection, and that participants’ details are accurate.

Genomics England works with industry through its Discovery Forum. The Forum provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape. Industry partners comprise pharmaceutical, biotech and diagnostic companies, and those specialising in laboratory and data analysis. These companies have joined the Forum to work in a pre-competitive environment with access to a selection of genomic and associated clinical data. Ultimately, the Discovery Forum aims to help the 100,000 Genomes Project and its partners to turn research findings into treatments, diagnostics and benefits for patients as soon as possible. There are currently over 100 members of the Forum.

As the Discovery Forum is a collaborative venture, no fees are levied on participating organisations. All members of the Forum are obliged to publish all findings and research at the point at which intellectual property for any product is protected. Participants in the 100,000 Genomes Project have been asked explicitly to give consent for commercial companies to access their de-identified genome and health data.

The Forum was created in July 2017 and allows industrial partners to report back to Genomics England on what aspects of the data are proving to be most useful to their research studies, what data is missing and how the data should be collected and developed further so it is captures what industry needs, in a format that is compatible with their research and data systems. These partners act as a ‘critical friend’ and have made many helpful suggestions to increase the likelihood of successful research in the future for all those using Genomics England’s landmark data set.

The lawful basis for processing Participant Data under the General Data Protection

Regulation (GDPR) used by Genomics England is legitimate interests as set out under Article 6(1)(f) of the GDPR. It is necessary for Genomics England to process Participant Data for its legitimate interests in carrying out medical research and in providing reports used by clinicians in their care of Participants.

It is necessary for Genomics England to process Participant Data for its legitimate interests in carrying out medical research and in providing reports used by clinicians in their care of Participants.

The processing is necessary to support and enable Genomics England’s legitimate interests in:

· Creating a new genomic medicine service for the NHS;

· Enabling new medical research on using genomics in health care, and on the causes, diagnosis and treatment of rare diseases and cancer.

The beneficiaries are:

· Participants through the work we do will influence their care;

· researchers and industry by giving them access to a unique ground-breaking resource of genomic data combined with life-course clinical data;

· and the wider public by accelerating the uptake of genomic medicine making it available to patients in the UK.

Genomics England’s target was to complete sequencing of 100,000 genomes by the end of 2018 – this was achieved by December 2018 - - https://www.newscientist.com/article/2187499-uk-dna-project-hits-major-milestone-with-100000-genomes-sequenced/

By April 2017 over 41,000 whole genomes had been sequenced and, with the aid of clinical data, the first diagnoses were announced:

• First diagnoses from the pilot phase https://www.genomicsengland.co.uk/first-patients-diagnosed-through-the-100000-genomes-project/

• First children diagnosed through the project https://www.genomicsengland.co.uk/first-children-recieve-diagnoses-through-100000-genomes-project/

• Financial Times article: https://www.ft.com/content/d2e21cea-d684-11e6-944b-e7eb37a6aa8e

By November 2018 109,611 samples had been collected, 91,100 genomes sequenced and 37,591 results returned to referring NHS Genomic Medicine Centres. Recruitment to the 100,000 genomes project is now completed, but analysis and return of results will continue throughout the period of this agreement.

By May 2018 the Genomics England Research Environment was established to allow research access to de-identified genome and clinical data received from NHS Digital. Thirty disease and cross-cutting GeCIP research domains were requested and approved, with over 1,300 GeCIP members given access to the Research Environment. Genomics England had also created the industry Discovery Forum to provide a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape.

By the end of October 2018 the fifth quarterly release of new data into the Genomics England Research Environment was achieved. This release included 71,860 genomes and primary clinical data for 85,070 participants. It also included de-identified clinical data received from NHS Digital for 60,110 participants, totalling 4.2m records. 1,821 GeCIP members from 387 institutions and 33 research domains now requested and been given access to the Research Environment, and 70 research projects have been approved. Alongside this there are 89 members of the industry Discovery Forum, including 10 full members.

Genomics England plans further releases of genomic and clinical data, including clinical data received from NHS Digital, into the Research Environment on the following dates, in order to continue support for, and to further develop, this ground-breaking resource:

• 28th Feb 19

• 30th Apr 19

• 31st Jul 19

• 31st Oct 19

Although the 100,000 genomes project has completed recruitment, Genomics England is committed to continue gathering life-long clinical data from the participants and making these available in the Research Environment.

Specific outputs over the period of this agreement are therefore to release updated genomic and clinical data for the 100,000 genomes participants into the Research Environment on the dates shown above.

Update December 2017

Over 41,000 Genomes were sequenced as of December 2017. Participant stories can be found at: https://www.genomicsengland.co.uk/alexs-story/

Genomics England has built upon its commitment to lead on Governments technology and innovation agenda by forging partnership with industry. Examples of this include a new industry collaboration with leading life sciences companies Inivata and Thermo Fisher Scientific to improve understanding of cancer.

Public Health England has announced that Whole Genome Sequencing (WGS) is now being used to identify different strains of tuberculosis (TB). This is the first time that WGS has been used as a diagnostic solution for managing a disease on this scale anywhere in the world. The technique, developed in conjunction with the University of Oxford, allows faster and more accurate diagnoses, meaning patients can be treated with precisely the right medication more quickly.

Genomics England has now engaged devolved nations and is recruiting participants from Scotland and Wales.

Update May 2018

Over 60,000 genomes have been sequenced and over 12,000 clinical reports have been issued to referring NHS Genomic Medicine Centres. Thirty disease and cross-cutting research domains have had their plans approved and now have access to 100,000 the Genomes Project Research Environment. The number of users with access to the Genomics England Research Environment is now over 1,300.

Twelve publications have arisen from or refer to the 100,000 Genomes Project during the last year, including:

• The 100,000 Genomes Project: bringing whole genome sequencing to the NHS. Clare Turnbull et al. BMJ 2018; doi: https://doi.org/10.1136/bmj.k1687 (24 April 2018)

• Identification of rare sequence variation underlying heritable pulmonary arterial hypertension. Nicholas W. Morrell et al. Nature Communications 2018;9; doi:10.1038/s41467-018-03672-4 (12 April 2018)

• Introducing genomics into cancer care. Sue Hill BRJ Surg 2018;105(2):e14-e15 (17 January 2018)

• Missense variants in the X-linked gene PRPS1 cause retinal degeneration in females. Alessia Fiorentino, Kaoru Fujinami, Gavin Arno et al. Hum Mutat 2017; doi:10.1002/humu.23349 (17 October 2017)

See https://www.genomicsengland.co.uk/category/updates/ and https://www.genomicsengland.co.uk/aboutgecip/ publications/ for details of news and publications.

Genomics England created the Discovery Forum in July 2017. It provides a platform for collaboration and engagement between Genomics England, industry partners, academia, the NHS and the wider UK genomics landscape.

Update November 2018

Over 109,000 samples have now been collected, 91,100 genomes sequenced and 37,591 clinical reports issued to referring NHS Genomic Medicine Centres. 71,860 genomes have been made available in the Genomics Engalnd Research Environment.

1,821 GeCIP members from 387 institutions and 33 research domains now have access to the research environment. There are now 89 members of the industry Discovery Forum, including 10 full members.

Latest publications include:

• Challenges in implementing genomic medicine: the 100,000 Genomes Project. Julian G. Barwell, Rory B.G. O’Sullivan, Laura K. Mansbridge, Joanna M. Lowry, Huw R. Dorkins. J Transl Genet Genom 2018;2:13; https://doi.org/10.20517/jtgg.2018.17 (11 Sep 2018)

• What will follow the first hundred thousand genomes in the NHS? Malcolm Grant & John Paul Maytum. Per Med 2018; doi:10.2217/pme-2018-0025 (20 June 2018)

• Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL. Jenny Klintman, Katerina Barmpouti, Samantha JL Knight et al. Br J Haematol 2018; doi:10.1111/bjh.15406 (29 May 2018)