Today we begin the series of interviews about Personal Genome Projects and this interview is with Professor Stephan Beck who is leading Personal Genome Project: UK.
Please introduce yourself. What is PGP in general and how is PGP-UK different?
I am a Professor of Medical Genomics at the UCL Cancer Institute and the Director of Personal Genome Project: UK (PGP-UK). My academic group is involved in projects investigating genomics and epigenomics of phenotypic plasticity in health and disease. We are a systems epigenomics group that is interested broadly in all aspects of it.
PGP-UK is a member of the Global PGP Network which currently includes four PGPs. The first one was founded by George Church in 2005 at Harvard University, then in 2012 Stephen Scherer started PGP-Canada in Toronto. In 2013, we launched PGP-UK at UCL. In 2014, PGP-Austria was launched by Christoph Bock in Vienna. These are the four projects that are currently active. There is a number of projects that are being planned and some of them are very close to actually launching as well but that will be announced when they are ready.
What was the motivation to start the very first one? What was the aim of George Church and then all other people to do it?
Well, you would have to ask him, I can’t speak for George. I think he got really frustrated by the fact that after the Human Genome Project went completely open access, all follow-up projects actually started some form of restricted access. Controlled by local and self-appointed Data Access Committees (DACs), restricted access has become a complicated ‘jungle’ of different access modalities that people need to negotiate through and, for some projects, it is almost impossible to even retrieve any data at all. Starting PGP made a clear case for continuing open access in human genomics. My own motivation is to also demonstrate, on my own genome, that sharing this data can be really beneficial and, if conducted properly, it should not be of excessive risk, if any risk at all.
Who can participate in the PGP-UK project and what is the incentive for people to participate?
Anyone who is over 21 year of age and who is either a UK citizen or permanent resident can participate. The age restriction is to ensure some degree of maturity so that people can understand what the implications are for them, their children (if they have or plan to have a family) and the rest of the family as well. To demonstrate that participants have understood the risks as well as the benefits, they need to pass a very stringent test. I invite everybody to take this test – even if not interested to participate) – but simply to see what level of knowledge is required to participate and to inform yourself what the risks are.
There are different reasons why people participate: in many cases it is a desire to support research, some participants are sort of information altruists who say it is information that they are very happy to make available because they made available other information about themselves already. Others participate because of the many benefits, i.e. not just to support research, but to learn about themselves. Contrary to other projects who recruit passive participants, PGP-UK recruits their participants as active collaborators who are expected to engage with us 3-4 times a year to update records and provide new data as well as feedback.
What kind of data do you generate for each participant?
We aim to generate genomes, methylomes and transcriptomes to our participants. This allows us to analyse the data for inherited and acquired variants as well as their functional consequences. For our first participants, we started doing whole-genome sequencing (WGS, 30X), whole-genome bisulphite sequencing (WGBS, 15X), 450K BeadChip analysis and RNA-seq (around 40 million paired-end reads). The resulting genome, methylome and transcriptome reports are reported back to participants along with all data. So far, we have reported back genome and methylome reports but the transcriptome report is still under development.
For medical research, the data are most powerful if combined with trait, phenotype, environmental and health data. For that, we had hoped that participants would be able to share relevant parts of their portable electronic NHS records that were to be provided to UK citizens and permanent residents by the NHS-funded Care.Data Programme which unfortunately has been put on hold. Until these data become available in electronic format, we do ask our participants to fill in questionnaires and collect the data that way. We also allow participants to upload data directly via their accounts. Participants can also choose to self-identify or remain anonymous. Direct uploads prompt warnings about identifiable information and reminders to remove it if intention is to remain anonymous. In that way, participants can choose which information is visible and to whom. By default, everything is visible to everyone.
Who and how can access data from PGP-UK?
In line with PGP philosophy, all the data will be made available free and unrestricted under open access. Ideally, we would like to make the data available in the same format and through the same public databases such as dbGaP and EGA that researchers are already familiar with from controlled access projects. Unfortunately, this turns out to be more complicated than anticipated and negotiations to this effect are still ongoing. Until a solution can be found for a single database to host all data, they will still be available under open access from different public repositories. For PGP-UK, these will be ENA for genome, methylome and transcriptome data, EVA for variant call data, ArrayExpress for BeadChip data and the PGP-UK web site for reports and all other data.
By the way, how many participants and how much data do you currently have?
We have 10,000+ registered for participation, 1000+ fully enrolled, 100+ in analysis and 10+ completed. The level of public interest in PGP-UK has been phenomenal but we had to pause further enrolment until additional funding has been secured. PGP-UK is free to all participants and, like the other PGPs, we have not yet received any public funding. For the time being PGP-UK is self-funded, based on donations and crowd-funding. There is a clear need though as there is no other open access linked genomic and phenotypic resource in the UK. So we will keep applying …
So far, we have completed and reported back to our first 10 participants, the PGP-UK10 and hope to follow the same success the Harvard PGP had with their PGP-10. Like they, a number of PGP-UK10 participants are likely to self-identify as I have already done as PGP-UK1, because I have the same motivation as George – if there should be any problems or backlash, they should come back to me in the first instance, and that’s fine. As a next step, we plan to publish our findings from PGP-UK10 and hopefully raise enough awareness so that funding agencies will change their minds.
What is your vision for the future of PGP-UK and PGP movement in general?
My vision is for PGP-UK to become a leading member of the Global PGP Network and key resource to accelerate and advance personal and medical genomics. To achieve that, we need increased acceptance and willingness by public funding bodies to support such projects which is currently missing. To date, none of the active PGPs in the USA, Canada, Austria and UK has received any public funding and PGP remains totally dependent on philanthropic donations. By publicising the important contribution PGP makes towards the expected transformation of healthcare and implementation of precision medicine though the use of omics data and by publishing our scientific findings from the first 10 PGP-UK participants, we hope to bring about these necessary changes.
PGP-UK is the first PGP that reports back incidental findings based on epigenetic variants, nobody else has done this before. This is a very exciting new aspect of PGP-UK and my vision is to work with regulatory and counselling bodies to develop the ethical, legal and social implications (ELSI) framework for epigenetic variants to be reported back in a similar way as it is already being done for genetic variants. To facilitate the identification and regulation of the first clinically actionable epigenetic variant would be a major achievement. We see ourselves as the pioneers for that and our first personal epigenetic reports were extremely well-received by our PGP-UK participants.
Another ambition of PGP-UK is to nationally role out Genome Donations which we introduced in 2015 as a new mechanism and choice for more open data sharing. The number of people in the UK and elsewhere who have their genomes sequenced for one reason or another is increasing vastly but only few if any of these genomes and associated data are being made available for research under open access. The concept of Genome Donation will overcome this limitation. It is based on the fundamental ownership of individuals over their genomes, irrespective of the terms and conditions under which they may have been sequenced. In practice, it means that individuals have the right to request a copy of their genomes which they can then donate to an approved project. Both, donating and receiving genomes are and should be subject to ethics approval and, to our knowledge, PGP-UK is the first project to have obtained ethics approval for receiving Genome Donations and the first two have already been received. Enrolment in PGP-UK is generally accepted in place of independent ethics approval for donating a genome as our enrolment procedure clearly demonstrates that individuals have understood the risks as well as the benefits of donating their genomes. In collaboration with the Global Alliance for Genomics and Health (GA4GH), we are now in the process of developing Genome Donations into a general mechanism for data sharing. In the UK, the largest sequencing effort is the 100,000 Genomes Project and we expect a good proportion of the eligible participants to be interested and willing to donate their genomes to PGP-UK and/or other projects once a mutually acceptable framework for Genome Donations is in place. The process has been initiated, so watch this space …
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