Long-read sequencing at Genomics England | LC26

Abstract
At Genomics England we are evaluating the potential role of long-read technologies in clinical whole-genome sequencing. Long-read technologies such as those developed by Oxford Nanopore Technologies offer the promise of comprehensive whole-genome sequencing, providing in a single test/experiment nucleotide variants and epigenetic modifications, alongside the potential to resolve large scale variation, and to uncover previously inaccessible parts of the genome. The possibility of such a comprehensive view of the genome is particularly appealing in clinical settings, and with platforms like the Oxford Nanopore PromethION sequencer, long-read sequencing at both speed and scale has become a realistic prospect. However, there is still a lack of large publicly available clinical long-read datasets, and this presents a problem for assessment of the technologies and the development of analytical tools. To this end, we have been building datasets using Oxford Nanopore PromethION sequencers since 2019 and have sequenced more than 15,000 PromethION Flow Cells. Here we present our experiences with Oxford Nanopore sequencing at Genomics England, moving from pilot studies to projects involving thousands of participants, across rare disease and cancer in several programmes. We describe our long-read datasets and our approaches to generating them, highlighting challenges unique to this developing technology and the solutions that we have chosen on our journey to long-read sequencing at scale. We introduce the pipelines and infrastructure that we have developed, how our strategies have evolved as the technology has matured, and how we have moved from sequencing in a single lab to distributed sequencing across multiple sites.

Biography
Adam is a Senior Bioinformatician, working on long-read sequencing at Genomics England for the past seven years. Prior to that Adam worked in range of academic institutions, including a PhD in computational biology at the University of Bergen, Norway.