Genomic medicine: ushering in a new era in healthcare
EMBL-EBI data resources are being used to deliver thousands of genetic diagnostics to patients every month
Credits: Karen Arnott/EMBL-EBI
Genomic medicine uses technologies such as genome sequencing to support healthcare. It has the potential to transform people’s lives by enabling quicker diagnosis – especially for rare disease and cancer patients, matching patients to the most effective treatments, and monitoring treatment response.
A number of European countries such as Finland, Norway, Denmark, France and the UK have active programs in genomic medicine. This case study focuses on one of the most advanced systems, the UK’s National Health Service (NHS) Genomic Medicine Service. This is the first in the world to offer whole genome sequencing as part of routine care, via a partnership with Genomics England.
Genomic medicine improves patients’ lives
Patients in England are already seeing major benefits from genomic medicine. Below are just a few stories of patients whose lives improved following genomic medicine interventions.
Many of these sequencing reports will generate new diagnoses with an immediate impact, enabling better advice for patients and relatives, fewer hospital visits, and more accurate care.
Rachel was diagnosed with a gastrointestinal stromal tumour (GIST) – a type of sarcoma – in her teens. For 15 years, she tried a number of treatments. Genomic sequencing revealed that she had a rare sub-type of the disease, caused by a glitch in her genes. This indicated that it could be hereditary, meaning that her family was eligible for screening. It also showed that Rachel was at a higher risk of developing other rare cancers, which she is now screened for annually. The new information also helped her doctors to identify which treatments would be the most effective for her.
63-year-old Alan had been misdiagnosed with a range of skin conditions all his life. Following genomic tests, he finally learned that he had Olmsted Syndrome, a very rare disorder causing abnormal growth and thickening of skin. His consultant was then able to advise on a suitable treatment to manage his condition. Within 24 hours of starting the treatment, Alan had progressed from being forced to crawl through his house to being able to stand and walk.
Genomics England sequenced over 100,000 whole genomes as part of the 100,000 Genomes Project and every one of these used EMBL-EBI data as a reference for analysis and interpretation. In addition, thousands of patients each month receive results from other kinds of sequencing from NHS Genomic Laboratory Hubs, which rely on EMBL-EBI data and tools.
Reference data is critical data
In order to interpret genomic sequencing results, clinicians need reference data – for example, to work out whether the version of a gene that a patient is carrying is common, or a rare mutation.
Genomics England and NHS Genomic Laboratory Hub workflows depend on EMBL-EBI data resources, and use these data in bulk. Every time the NHS analyses sequencing data to return a diagnostic report to a patient, it relies on the Ensembl gene annotation database, and tools like Variant Effect Predictor, which determines the effect of changes to the genetic code. Without the reference data held at EMBL-EBI, genomic tests would not be able to offer insights into patients’ conditions or suitable treatment.
“Part of EMBL-EBI’s mission is to provide freely available data and bioinformatics services, open to anyone,” explained Ewan Birney, Director of EMBL-EBI and Deputy Director General of EMBL. “Genomic Medicine services built on reference data are a perfect example of the value our open resources create for users and the benefits this can bring for patients.
“Without the reference genomic data managed by EMBL-EBI, it’s impossible to interpret genomic tests. It would be like trying to solve a puzzle with billions of pieces from slightly different versions of the same jigsaw, with no guiding picture.”
Applying the latest tech in precision medicine for cancer
Researchers at EMBL-EBI also work with Genomics England to explore the potential of genomics for cancer precision medicine. Because each patient’s cancer features a unique constellation of mutations, genomic sequencing can help to map these and guide treatment decisions.
The Cortes-Ciriano group at EMBL-EBI uses the latest generation of sequencing technology, called long read sequencing, to get insight into sarcomas, brain tumours, ovarian cancer and leukaemias.
The sequencing is done in close collaboration with Genomics England and EMBL-EBI is contributing its extensive expertise in data analysis, as well as developing new tools to help overcome the relatively high error rate from long-form sequencing compared to previous methods. One such tool, developed by the Cortes-Ciriano group, is SAVANA, a new algorithm designed to detect somatic structural variants.
What is long-read sequencing?
The genome of most organisms is too long to be sequenced as one continuous string. As the name suggests, long-read sequencing technology enables the production of ‘reads’ that are considerably longer than those resulting from older technologies. This has many advantages: for example, it means reads are easier to assemble, and the technology can sequence parts of the genome that were inaccessible before. The technology also has the potential to be highly portable, scalable, and significantly less costly than other alternatives, so it has significant potential for clinical applications.
Training the genomics workforce
But genomic medicine goes beyond sequencing technology and large data sets. It also needs a workforce with the skills required to build clinical bioinformatics workflows and to interpret results.
EMBL-EBI alumni have gone on to work at Genomics England, implementing clinical workflows based on the tools they stewarded during their time at EMBL-EBI.
Moreover, EMBL-EBI is part of a consortium set up by NHS England to deliver one of the world’s first Genomic Medicine Masters courses. The EMBL-EBI Training team co-developed two of the modules, including the advanced bioinformatics module, to ensure the skills required to work with genomic data were transferred from researchers into the NHS workforce. To date, the ongoing course has trained over 1,500 clinical decision makers including registrars, consultants, nurses, midwives, pharmacists, bioinformaticians, laboratory scientists, and other allied health and scientific professionals.
“To get genomics into the clinic, current and future healthcare professionals need to feel confident using genomics and big data in their day to day work,” said Jo McEntyre, Associate Director of EMBL-EBI Services. “The training material we deliver for the Genomic Medicine Services is a great example of how EMBL-EBI is working with collaborators in Europe and beyond to help make this happen.”
Reference data, analysis tools and training are essential for bridging the gap between research and healthcare, and bringing genomic medicine into the clinic. Because EMBL-EBI resources are open source, countries around the world embarking on this journey can make use of them in an appropriate manner for their needs and systems.
