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

Whole-genome sequencing (WGS) can identify variants that cause genetic disease, but the time required for sequencing and analysis has been a barrier to its use in acutely ill patients. In the present study, we develop an approach for ultra-rapid nanopore WGS that combines an optimized sample preparation protocol, distributing sequencing over 48 flow cells, near real-time base calling and alignment, accelerated variant calling and fast variant filtration for efficient manual review. Application to two example clinical cases identified a candidate variant in <8 h from sample preparation to variant identification. We show that this framework provides accurate variant calls and efficient prioritization, and accelerates diagnostic clinical genome sequencing twofold compared with previous approaches. A streamlined sequencing process enables identification of disease-causing variants in the clinic within 8 hours.

Automated summary

This study developed an ultra-rapid nanopore whole-genome sequencing method, which efficiently identified disease-causing variants within a short period of time. The approach included optimized sample preparation, near real-time base calling and alignment, accelerated variant calling, and fast variant filtration. The results demonstrated accurate variant identification and efficient prioritization, significantly reducing the time required for clinical genome sequencing.