Festival of Genomics 2019 – The State of Genomics Today
This article originally featured in the event guide for our 2019 Festival of Genomics.
The life sciences sector is an incredibly fast-moving field, and nowhere is that represented more than in genomics, which of late has seen vast changes to several key areas of research. The introduction of multi-omic research, the advancement of AI and machine learning to improve nearly every aspect of sequencing and data analysis, are just some of the big changes that will only become more prevalent in the future. To make sense of some of the biggest trends and news stories this year, we spoke to Angela Douglas MBE, Scientific Director of Genetics Laboratories at Liverpool Women’s Hospital, for her opinions on the changing nature of genomics and the trends to watch out for.
What to You Has Been the Biggest Genomics News in 2018?
For us, the biggest news this year has certainly been reaching our target of sequencing 100,000 genomes through the NHS. When we first embarked on this project in 2014, I think a lot of people thought we’d never achieve the 100,000 goal. This month, we did it. Looking forward, the impact of having that information for our patients’ health and treatment will be huge.
The project is doing its part to establish the UK as the home of a unique world-leading genomics programme improving patient lives, ensuring the UK is the home of world-leading genomics companies that will work in partnership with the NHS and its academic research partners, and stimulate the development of diagnostics, devices, medicines and treatments based on a new understanding of the genetic and molecular basis of disease.
The 100,000 Genomes Project has already brought significant transformations to the genomic laboratory services, with more access to genomic sequencing than ever and the ability to sequence 20,000 known genes at the same time.
Despite this there are still some big logistical and ethical obstacles to implementing whole genome sequencing as a diagnostic test. First, we must be able to confidently identify a pathogenic mutation from the millions of variants per genome. Second, we also need an increased knowledge of ‘normal’ variation. The Regional Genetics Services analysis has so far been restricted to known genes linked to the patient phenotype in the form of gene panels or whole exome sequencing.
Overall, however, I am confident that we can overcome these obstacles and that in the future genomics delivery in healthcare will provide a more personalised and holistic approach for patients with rare diseases and cancer.
We can already see research similar to the 100,000 Genomes Project being taken up by other countries around the world. Other countries are trying to follow the world-leading research we have undertaken. Certainly the project leaders in NHS England and Genomics England are being invited to talk around the world about our achievements in the project, its benefits to patients, and how we’re embedding all the learning from the project into developing our new Genomic Medicine Service.
The 100,000 Genomes Project was Recently Completed. What’s Next?
MP Matt Hancock at the Conservative Party’s annual conference recently announced the upcoming Five Million Genome Project. Of those five million, one million will be delivered by the NHS. Of this, 500,000 will be delivered through the national test directory and the testing we’re undertaking on patients coming into our Genomics Medicine Service. A further 500,000 will be participants who have provided their DNA to the UK biobank, giving us a cohort of potentially normal controls, which will help us look at the whole prevention and prediction element of genomics in public health. The other four million for the project will be through partnerships with academia and industry partners, attempting to find out more about the genome, about discovery, and about new drugs.
As far as I’m aware, much of this work will be targeted on cancer and personalised medicine, as I think that’s where we’ll start to have some real impact.
In Your Opinion, has the State of Genomics Gotten Better or Worse over the Last Decade?
It’s definitely improved! When we first started the 100,000 Genomes Project we collected a lot of external quality assurance data from our labs as they worked. Back then, the quality of DNA extracted, the way it was processed and how the samples were handled wasn’t as good as this could have been, and over the course of the project we’ve been able to optimise DNA extraction and the quality of DNA, optimise our sample handling, and optimise our logistical pathways so that we can get our samples to the labs quicker and DNA extracted at the highest quality to get analysable whole genome sequences out at the other end.
Globally it’s much the same – in some of the more research-affluent countries, and certainly in America, we have seen genomics, maybe not whole genome sequencing but certainly exome sequencing and large panel testing, being implemented into healthcare where there’s an insurance policy backing that and where individuals can pay to have those tests done. This is certainly the case in some EU countries which are ahead of the UK as far as exome sequencing of rare disease cases is concerned, though I think the UK definitely leads in the field of cancer.
How Will Brexit Affect the Genomics Industry?
So far it’s been a rollercoaster! There’s so much uncertainty. There are two big issues I think which will impact genomics, the first being regulation. We currently follow European Union regulation, and when we leave the EU those rules will end for the UK. Currently, the NHS is working with the Medicines and Healthcare Products Regulatory Agency (MHRA) to make sure we’re building a regulatory framework around genomics, around medical devices, and around testing, so when we do come out of the EU and aren’t under their regulations we have an appropriate framework to still maintain safety for patients going forward.
The second thing is the EU research networks. UK leaders in rare disease have traditionally led some of these EU reference networks (ERNs) for different rare disease specialties. What we’re currently being told is that after Brexit NHS organisations and UK academics won’t be able to lead those networks any more, they’ll have to pass that over to EU colleagues even though they’re global experts. There’s even a question as to whether we’ll even be allowed to maintain that partnership.
The importance of these networks is that they provide us with an opportunity to look at variants or changes in very rare diseases, and to start to have a global conversation, or at least a pan-European conversation, and begin to understand the change in the genome and how it impacts on the clinical features and manifestations we see in our patients. That’ll be a big loss to UK patients if we can’t access or lead those networks in certain rare disease areas.
What Future Trends or Innovations are You Excited About? Are There Any That Healthcare or Pharma Companies Should be Aware of?
I’m really excited about artificial intelligence. This is because at the moment the NHS is generating a lot of information without any real analysis being undertaken. With increased AI power and smarter algorithms, we can start to look at trends, detect early warning signs in patients, or use wearables to monitor someone’s softer health statistics. With future innovations I think we’ll be able to bring all this data together and be able to do some real research into prevention, and start to analyse big data and understand population health better.
In terms of business and industry, I definitely think that’s the biggest trend for the informatics and digital industries as they relate to healthcare. For the companies that are producing the machines we use in our labs, I think the continuing advancement of robotics will be very important.
Multi-omics is one of the Latest Big Trends in the Life Science Sector. Has it Affected You and the NHS? How Will it Affect You in the Future?
Right now, we’re only just starting to look at “-omics” samples other than genomics. At the moment we are analysing the whole genome, but some of the results are showing variants of unknown significance. What we really need to be doing is setting up functional studies in our labs to be able to identify the significance of those variants. We need to find out whether they have any impact on a protein, whether that protein has an impact on the metabolism, whether we’ve found a new metabolite which could manifest itself in the phenotype we are seeing in the patient. This would allow us to start to understand the action of those variants of unknown significance.
There’s another innovation that hasn’t been fully implemented yet, which I glimpsed at a conference on medical physics and clinical engineering I had the pleasure of speaking at earlier this year. That was radiomics, which was first brought to attention in 2009 and hasn’t really been spoken about since.
Radiomics works in exactly the same way as genomics, in that when our patients have CT scans, ultrasounds, MRIs, or other types of scan, key markers exist which can be picked up by experts who work on those images, using AI, and bringing the information together with genomics to see if they can actually make predictions about a patient. For example if we’re scanning for cancer, radiomics could allow our experts to use markers on the scan to predict whether that patient will relapse, or how that tumour will progress. Bringing that sort of information together with genomics and building algorithms to facilitate it will enhance our patient care.
The “CRISPR Twins” Story was One of the Biggest of the Year. What is Your Take on That?
I don’t really know a lot about the technology; nevertheless I have some real ethical concerns about that story. Although the technology used to edit the embryos of those twins’ DNA is established, and CRISPR is a good research tool, editing the genome hasn’t really been validated to see what the long term effects are in infants. From what little we know about the genome, it’s not just about the effect the gene has on the clinical phenotype, it’s the effect that gene has on other surrounding genes and the polygenic effect on individuals that we really don’t understand, and if we change one gene, we really don’t know what the unintended consequences are downstream and the way that might have a reaction with other genes.
We may know that a mutation in a given gene will cause a disorder, but we don’t know what effect editing that gene to repair the mutation or variation that’s occurred will have on the way that gene enables interaction with other genes.
You’re One of the Key Speakers at our Festival This Year. Do You Think Giving Such Talks, and Disseminating Knowledge Throughout the Community, Forwards the Cause of Genomics Generally?
I do! I think we need to get out and spread the word as widely and often as possible. Life science is a constantly changing field, and one where everyone might hold a little bit of information, but not the whole picture. By coming together, we can share information so everyone can see the bigger picture. Listening to the ways that others are working really helps us improve our own processes.
What First Inspired You to Start in Genomics?
I’ve actually worked in genetics since 1980, believe it or not! I’ve been in the NHS now for 38 years and I’ve always worked in genetics. I’ve always worked within the NHS because altruistically I want to know that I’m making a difference in patient care – and I believe you have to have a purpose in life, and that’s why I work here, because it gives you a purpose and a sense of helping people.
I was inspired by a relief biology teacher – my normal biology teacher was actually very boring, but she became pregnant and we had a relief teacher. She was only with us for six months, but she was so enthusiastic about genetics that she actually inspired me to study genetics as a degree. I went to UCL, and took one of the first pure genetics degrees there, and I have never looked back. It’s always been what I wanted to do. The one thing about genetics and genomics is: it’s constantly changing. No two days are the same. You’ll never get bored, because the technology and the knowledge is constantly changing.
As we glean more knowledge from the newer technology, we can help more and more people. That’s why I came to work in genetics in the first place.