22-23 - GENOMES: Next gems

Last November, a British research team published a study that offered a tantalising preview of how next-generation genomic sequencing promises to transform medicine – and benefit millions of patients with a wide range of diseases.

The study was the first to emerge from the 100,000 Genomes Project, which was established in 2013 with the goal of sequencing whole genomes from 100,000 NHS patients. By analysing the genes of 4,660 participants in that project, researchers were able to diagnose rare diseases in 25% of patients, 14% of which were discovered in areas of the genome that might have been missed by more conventional testing methods.

The study also uncovered three new disease-related genes and 19 previously uncovered associations between genes and rare diseases, the researchers reported in the New England Journal of Medicine. Notably, the study also found that 25% of the diagnoses had immediate clinical ramifications for patients and their families.

Next-generation sequencing (NGS) technologies are making it faster and more affordable than ever before to obtain actionable medical data from genomic samples, enabling much more than just improved diagnoses of rare diseases. Insights derived using NGS are also improving approaches to population health and informing disease-management strategies.

Three trending applications are redefining the power of NGS:

NGS has grown to be a popular technology for the genomic surveillance of infectious diseases like COVID-19. It has enabled the identification of mutant strains and novel coronavirus mutations, the study of infectious disease therapy resistance, among others.

During the COVID-19 pandemic, NGS was used to decode the first SARS-CoV-2 sequence, which supported the creation of additional tools to help slow the pandemic. The initial sequencing provided researchers with the information needed to conduct basic research on effective assays to detect the virus, and it also enabled the development of vaccines.

Public health officials are continuing to turn to viral surveillance research using NGS to develop strategies to reduce transmission and infection. NGS has quickly emerged as a promising tool in the race against new viral variants and will continue to play a crucial role in predicting and preventing future outbreaks.

All cancers start with mutated genes. Gene mutations can be inherited or occur from environmental exposure. Studying genomics, genes and gene function gives researchers and clinicians line of sight into how mutated genes impact cancer symptoms, tumour progression, treatment responses and health outcomes.

Whole exome sequencing (WES), a method gaining popularity in cancer research, provides researchers with the ability to gather and bank an entire exome for future reference. As it is widely accepted that about 85 percent of disease-causing variants are found within the exome, WES provides a good cost vs. benefit option for researchers in terms of the amount of biological insights obtained from a single sample.

WES also can identify single-nucleotide variants, insertions, deletions, and copy number changes – all of which are important for understanding cancer growth drivers.

The potential adoption of NGS as a standard of care for oncology patients reflects how the industry is advancing to provide rapid, comprehensive information to patients and providers. In the United States, some cancer centres are now offering in-house NGS testing to patients. But the wealth of data generated through NGS-based testing doesn’t stop there.

It goes beyond individual patients – connecting them to available clinical trials that advance research and strengthen the reservoir of knowledge for the entire cancer community at large to benefit future patients.

Not all cancers are the same. With the help of biomarker identification via NGS testing, more precise treatment options can be uncovered for patients depending on their cancer type and stage. The discovery and identification of new, targetable biomarkers in research is driven by comprehensive tumour profiling using NGS.

In therapeutics, biomarker identification not only helps to prevent costly and ineffective treatment, but it can also generate actionable intel to inform other solutions with maximum benefits for a patient.

Biomarkers are integral to medicine in general and their understanding is an important step toward precision medicine. The ability to connect the right treatment to the right patient at the right time has potentially life-saving benefits.

While NGS has advanced significantly over the last decade, challenges remain across the workflow, from sample preparation to data analysis. Overcoming these obstacles will be critical to ensuring the wide adoption of the technology and to maximise its impact.

Nevertheless, NGS technologies will continue to be a mainstay of genetic research and discovery. New breakthroughs are helping more researchers sequence samples they never thought they could.

With continued acceleration and dynamic adoption, NGS holds the power to realise breakthroughs for many generations to come.