Shaping the Future of Genomic Medicine

The evolution of genomic technologies has fueled improvements in diagnostic and treatment options for a range of medical conditions, from cancer to rare diseases. Recent innovations and initiatives are helping to overcome some of the remaining limitations in the field and expand the reach of genomic medicine. 

In this interview, James Brayer, director of strategic product management at Oxford Nanopore Technologies, delves into some of the current obstacles hindering the widespread adoption of genomic medicine and highlights how nanopore-based sequencing can help to address them. James also shares his views on the future trajectory of genomic medicine and what it could mean for patients.

Anna MacDonald (AM): Can you tell us about some of the challenges limiting the potential and wider adoption of genomic medicine?

James Brayer (JB): Genomic technologies have been tremendously effective in certain cases, such as characterising genetic diseases in newborns or rare diseases. However, the diagnostic yield – the success rate in solving these challenging cases – using exome sequencing or even whole genome sequencing still leaves a large fraction of people without answers. Mounting evidence suggests that one major limitation of conventional next-generation sequencing tools is that these short-read technologies miss many elements that cause or contribute to diseases, such as complex structural variants, epigenetic marks, repetitive stretches of DNA, and more.

AM: How is Oxford Nanopore working to address these challenges? Can you tell us about some of the solutions being developed to help advance this field?

JB: Clearly, the benefits of genomic medicine must be expanded to more patients. We developed our nanopore-based sensing technology with the goal of giving scientists and clinical researchers the most comprehensive view possible of each genome. What’s missed by other sequencing platforms can matter a great deal for a thorough understanding of health and disease. Our technology aims to address these gaps by giving scientists the option of generating reads long enough to span and resolve complex structural variants, repeat expansions and other genomic elements that cannot be characterized accurately with short reads only. We also allow for direct RNA sequencing and simultaneous methylation detection, both of which could provide clinically relevant data to help explain the biological underpinnings of a disease.

AM: What impact could nanopore-based sequencing have on patients? What advantages does it offer over alternative sequencing methods?

JB: The primary advantages of our nanopore-based sequencing technology are speed, flexibility, and accessibility.

Speed: Nanopore users can begin analyzing their data very quickly because base calling and alignment can be performed while the sequencer is reading DNA. Scientists at Stanford reported using ultra rapid nanopore sequencing to identify the genetic cause of disease in critically ill patients, going from initial blood sample to final results in less than eight hours. In a separate research effort, scientists paired nanopore sequencing with deep learning to classify central nervous system tumors in just 40 minutes, making the approach potentially useful during surgery.

Flexibility: While other sequencers produce only short reads or only long reads, nanopore-based sequencers allow users to generate short or long reads, whichever works best for their needs. Additional flexibility is added with capabilities for direct RNA sequencing and for methylation detection that occurs at the same time sequence data is produced, eliminating the need to run additional samples to generate epigenetic data.

Accessibility: Nanopore-based technology is more affordable than any other sequencing technology, and its portable size makes it amenable to sequencing samples wherever they are, rather than requiring a large laboratory.

Taken together, these advantages make it possible to streamline genome sequencing and analysis, producing haplotype-resolved assemblies when needed. As nanopore-based sequencing is adopted in more clinical research settings and validated in CLIA-certified laboratories, this will help get actionable information into the hands of physicians.

AM: Oxford Nanopore recently launched a sequencing research project with Genomics England. Can you give us an overview of the project and what you hope to achieve?

JB: We kicked off a research partnership with Genomics England to tackle rare disease cases that have eluded diagnosis. Our colleagues at Genomics England plan to study as many as 7,500 publicly available samples with the goal of solving more undiagnosed cases, better characterizing disease-related genes, and identifying variants that have been missed by previous sequencing platforms.

AM: How might projects such as this help to shape the future of genomic medicine?

JB: Ultimately, we hope the results from the Genomics England project and others will serve as much-needed resources for the rare disease community. As we can capture more and more of what’s missed by older generations of sequencers, it should be possible to provide more complete answers that will make a difference for understanding what’s going on with a patient – and eventually guide clinical decision-making. This should dramatically expand the benefits of genomic medicine.

AM: What do you see in store for genomic medicine in the next few years?

JB: The success of sequencing programs for rare diseases in the largest academic medical centers today should fuel similar efforts in smaller healthcare systems and hospitals in the coming years, making genomic medicine more equitable. We also expect to see more routine exome and whole genome sequencing as part of the diagnostic process for challenging cases, perhaps becoming one of the first tools used, instead of one of the last. At Oxford Nanopore Technologies, we are actively working to commercialize sequencing tools for clinical use, and we hope those will begin making a difference for patients in mainstream medicine in the next few years.

About the interviewee:

James Brayer is director of strategic product management at Oxford Nanopore Technologies.

James Brayer was speaking to Anna MacDonald, Senior Science Editor for Technology Networks.