In 2013, the UK government launched an ambitious project called the 100,000 Genomes Project that intended to accelerate genomic research on a national and global scale. The principal objective was to sequence 100,000 genomes to demonstrate the feasibility and utility of clinical genomics within the NHS. James Duboff, Strategic Partnerships Director at Genomics England, added that they wanted to make this data available to multiomic researchers across academia and industry to bolster new discoveries and innovations in genomics.
Duboff acknowledged the enormity and cost of the 100,000 Genomes Project, yet by 2018, Genomics England reached the 100,000 mark. Of the 100,000 participants, 32,000 had cancer. For every cancer participant, both their somatic and germline genome were analysed. The somatic genome offers insight into what is driving the tumour whereas the germline genome indicates any predisposition the patient has to cancer.
In an exit questionnaire asking clinicians whether the 100,000 Genomes Project led to a change in diagnosis or treatment, over 50% said yes in the case of cancer. Duboff said: “In over 50% of cases, there was a significant benefit that came from whole genome sequencing, both their somatic and germline in either a better treatment, enrollment into a clinical trial or triage to the most appropriate kind of treatment of their cancer, which is pretty fantastic.”
This project is key to tackling the diagnostic odyssey: a phenomenon describing the frustration of receiving multiple misdiagnoses and moving back and forth across the health system to try to find an appropriate specialist before receiving an accurate diagnosis. This issue is particularly common in rare disease patients who see multiple specialists and try different therapies and treatments for an average of 10 years before an accurate diagnosis is given. By the time the patient is given a correct diagnosis, it is likely that the patient’s condition has worsened, and they are in decline. At this stage, they are usually passed the point where therapy will make a maximal impact.
This predicament encouraged Duboff to increase efforts to recruit children and adults with rare diseases. Genomics England asked clinicians to go above and beyond; they were asked to conduct whole genome sequencing, purify RNA and protein from the individual, and recruit the patient in question and a family member into the project.
In the case of rare diseases, the project achieved a 20% diagnostic yield for rare diseases. While this initially appears low, Duboff mentioned that this later increased to 30% through research reanalysis. Duboff reiterated that this has been a game changer for many rare disease sufferers.
Moving forward, Genomics England aims to sequence newborn babies using umbilical cord blood to detect over 300 treatable conditions at birth. This could potentially prevent these babies from experiencing the 10-year diagnostic odyssey. Future plans include using long-read sequencing to fill in any sequencing gaps and give more clarity on certain variants. To achieve this, Genomic England will rely on its existing partnerships with companies specialising in proteomics like Olink and Oxford Nanopore.
