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The 100,000 Genomes Project has finished: what were the challenges and what comes next?


This week, the Health Secretary Matt Hancock announced that the 100,000 Genomes Project has reached its goal of decoding 100,000 genomes from NHS patients. We take a look at some of the challenges that had to be overcome to reach this point and ask what happens next?

Posted on 07 December, 2018 by Dr Sam Dick and Dr Keith Bradnam

Computer rendered impression of DNA strands.

Image: Computer rendered impression of DNA strands.

Gene sequencing has come a long way since 2003, when the first human genome was fully sequenced. At the time, it took more than 10 years and cost more than £2 billion. Today, thanks to next-generation sequencing, we can sequence a whole genome in a day at a cost much closer to £700, and this is getting cheaper and faster all the time.

Incredible improvements in technology over the last decade have led to an explosion in genomics research, giving birth to Genomics England's 100,000 Genomes Project which reached the finish line this week.

Initiated in 2013, the 100,000 Genomes Project aimed to establish the use of whole-genome sequencing in the NHS, driving the changes needed to adapt the approach more widely. This project has supported the development of new infrastructure and the education of a workforce that is now ready for the integration of genomics into the NHS.

Cancer genomics

The primary goal of this project was to sequence the genomes of around 75,000 NHS patients in England, with a focus on those with rare diseases or cancer.

Approximately a third of patients involved in the project have had the genome sequence of a tumour sequenced in addition to a genome from their healthy cells. The combination of healthy and tumour genome sequence from the same patient accounts for half of all genomes in the 100,000 Genomes Project.

Sequencing cancer genomes underpins a lot of the science that happens at The Institute of Cancer Research, London. Earlier this year we became the first institute in the UK to adopt use of the NovaSeq genome sequencing technology by Illumina, allowing us to dramatically increase our ability to decipher the genetic code of tumours.

Understanding the genetic basis of individual cancers allows for the selection of better treatments for patients based on their individual tumour genetics. This could help minimise the side-effects of common chemotherapies and lead to intelligently-designed clinical trials that could yield better outcomes.

So what have been the challenges of bringing whole genome sequencing to the NHS?

Getting the right samples

A significant challenge for the project was changing the way that samples were collected from patients and prepared for sequencing.

Historically, tissue samples have been fixed in formalin, a chemical that preserves tissue but is damaging to DNA. This makes many existing samples unsuitable for sequencing and meant that a radically new approach was needed for whole genome sequencing.

Genomics England worked with a number of partner organisations to drive changes in sample processing storage and transport, going on to call for collection of fresh tissues as a routine part of all cancer diagnoses. These samples are now prepped at local hospitals before being sent to specialist centres for sequencing and analysis.

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Dealing with the data

The next challenge came from the sheer volume of data produced by sample analysis and gathered through electronic health records. This is particularly difficult because data is being sent from a number of different centres, each with their own electronic methods of recording and storing data.

Successfully bringing whole genome sequencing into the current healthcare structure needs automated approaches to analysing the data – which means the data going in must be as standardised and uniform as possible.

Genomics England developed data models using systems that are recognised internationally to help this.

This combined with significant investment in local infrastructure and collaboration between NHS England, NHS Digital and data specialists at The Farr Institute has led to novel solutions to dealing with a huge range of data from a number of sources.  

Interpreting the data

A further challenge is knowing when a mutation is likely to be the cause of, or a risk factor for disease. People’s genomes vary naturally, and most mutations are unlikely to have any negative health effect. It is crucial that we classify mutations consistently across the country for whole genome sequencing to be useful in the NHS.

Genomics England has produced automated techniques for analysing different variations which can then be discussed by teams of specialists.

These standards are being developed by specialist teams for both rare diseases and cancer – optimising the use of staff, expertise and technology while aiming to support safe clinical practice that does not lead to over or improper diagnosis of individuals.

Crossing the line

The 100,000 Genomes Project has led to significant changes in NHS genomics infrastructure. Initial steps include the creation of 13 NHS Genomic Medicine Centres with samples supplied by more than 90 recruiting hospitals.

The infrastructure for delivering whole genome sequencing has developed massively and the genomics workforce has been expanded and upskilled to deliver genome sequencing on a larger scale.

Health Education England has also developed genomics training for the wider NHS workforce, aiming to truly embed genomics into routine healthcare.

The project took five years from inception to reach the halfway point which was achieved back in February. It is impressive that just nine months later, the final target has been reached.

What comes next?

It is clear that the 100,000 Genomes Project has catalysed the process of bringing genomics to routine healthcare. With the government increasingly focused on personalised medicine, early diagnosis and technology such as artificial intelligence, now is the perfect time to integrate whole genome sequencing into routine healthcare.

The NHS Genomic Medicine Service plans to provide patients with access to genomic testing from next year (2019). In September, leading childhood cancer experts at the ICR urged the NHS to use this opportunity to dramatically scale up access to genetic sequencing for children.

Our leading scientists and doctors called for a major upscaling in genetic sequencing for children with cancer, to understand patients’ disease better and help direct them to clinical trials that could offer more precise treatment.

The completion of 100,000 genomes marks the end of a chapter rather than the end of the story and earlier this year a new target was announced for the NHS to sequence one million genomes over the next 5 years.

Successfully delivering genomic medicine in the NHS will not only deliver better outcomes for patients, but also contribute to a wealth of information to drive the treatments of the future – giving us the power to diagnose and treat patients faster and in kinder, more efficient ways.


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