Publication Date
7-1-2022
Journal
Nature Biotechnology
DOI
10.1038/s41587-022-01221-5
PMID
35347328
PMCID
PMC9287171
PubMedCentral® Posted Date
3-28-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Chromosome Mapping, High-Throughput Nucleotide Sequencing, Humans, Nanopore Sequencing, Nanopores, Whole Genome Sequencing, DNA sequencing, Genetics research, Computational biology and bioinformatics
Abstract
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 inprioritization, and accelerates diagnostic clinical genome sequencing twofold compared with previous approaches.
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