Two new papers further demonstrate the role adaptive sampling could play in understanding genetic disease

Two new papers published in Nature Biotech today, from teams at the University of Nottingham and Johns Hopkins University, demonstrate the use of real-time nanopore sequencing and adaptive sampling for targeted sequencing without the need for upfront sample preparation. The papers describe methods that enable real-time electronic selection of molecules of interest which could have major implications in how genetic diseases are understood and diagnosed.

Payne et al. have developed Readfish and used it to show enrichment of specific regions of the human genome, and of low-abundance organisms in mixed populations without prior knowledge of sample composition.

They’ve enriched targeted panels comprising 25,600 exons from 10,000 human genes and 717 genes implicated in cancer, identifying a single fusion event responsible for a specific type of cancer in less than 15 hours. Read publication.

Meanwhile, Kovaka et al. developed UNCALLED — a novel raw signal mapping algorithm that enables adaptive sampling to enrich sequencing of a collection of 148 human genes associated with hereditary cancers to 30X coverage on a single MinION flow cell. This enabled robust structural variant detection with more than double the number of SVs detected than with 50x coverage whole-genome short-read sequencing, as well as accurate small variant calling and DNA methylation profiling. Read publication.

Targeted sequencing, or selecting regions of interest from a sample, typically involves significant manipulation of DNA prior to sequencing. This can involve PCR steps, Cas-mediated enrichment or hybridisation capture, each of which can add hours or days to the preparation and hands-on time, as well as additional cost. By selecting molecules in real time during the sequencing process, these steps are negated, making the process simpler, maintaining DNA modifications present in the sample, and accelerating delivery of answers to biological questions.

Be sure to tune in to the Nanopore Community Meeting this week to hear more on adaptive sampling from a number of speakers, including our opening plenary – Danny Miller, University of Washington.