Accelerated identification of disease-causing variants with ultra-rapid nanopore genome sequencing

Abstract

Whole-genome sequencing can identify variants that cause genetic disease, but the time required for sequencing and analysis has been a barrier to its use in critical care settings. Using nanopore sequencing, we developed a pipeline that was shown to identify clinically actionable genetic variants in as little as 7 hours 18 minutes. To achieve this, we accelerated sample preparation, leveraged the full capacity of PromethION 48 sequencing, developed a bioinformatics pipeline with near real-time basecalling and alignment plus accurate variant calling, and customised variant prioritization. Here, we will discuss these optimisations in detail.