Danny E. Miller from the University of Washington spoke at London Calling on the clinical applications of long-read sequencing. The title of this session was “Long-read sequencing as the future of clinical genetic testing.” Miller started with three points. The first was that long-read sequencing will change clinical testing within five years. The second reason is that long-read sequencing will reduce barriers to accessing comprehensive testing, making testing more equitable. The third is that all this will happen even if the cost of generating other data types falls to $0! Miller explained that the current testing methods are inefficient, requiring multiple visits, samples, and specialists. Clinical testing does not capture all types of disease-causing variation, Miller said, with short read sequencing. Finally, Miller said that labs must maintain competency for multiple tests… and this is expensive. Miller showed the Integrative Genome Browser (IGB) data by comparing R9 and “Q27” nanopore data, emphasizing quality improvement. Haplotype-resolved assemblies will identify more disease-causing variants. Miller said that new simplified workflows will be more efficient and will reduce overall cost. Miller shared case studies where long-read sequencing can be used as a single test to replace multi-step testing. Variants can be phased with nanopore sequencing even without parental samples. Some of the challenges Miller noted include improvement in databases of control variants for diverse populations. Automation is needed to facilitate sample handling, library preparation, and loading. Miller emphasized that robust tertiary analysis pipelines that utilize all aspects of long-read sequencing (methylation, phasing…) are needed. To realize the potential of long-read sequencing in the clinic, Miller said engaging payers to support a single sample workflow and resources for pre-test counseling and discussing complex results are needed. I watched Miller present previously, and this was another easy-to-follow session about long-read sequencing in clinical testing.
