Accelerated Identification of Disease-causing Variants with Ultra-rapid Nanopore Genome Sequencing

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2022 Mar 29

PMID 35347328

Authors

Sneha D Goenka

John E Gorzynski

Kishwar Shafin

Dianna G Fisk

Trevor Pesout

Tanner D Jensen

Jean Monlong

Pi-Chuan Chang

Gunjan Baid

Jonathan A Bernstein

Jeffrey W Christle

Karen P Dalton

Daniel R Garalde

Megan E Grove

Joseph Guillory

Alexey Kolesnikov

Maria Nattestad

Maura R Z Ruzhnikov

Mehrzad Samadi

Ankit Sethia

Elizabeth Spiteri

Christopher J Wright

Katherine Xiong

Tong Zhu

Miten Jain

Fritz J Sedlazeck

Andrew Carroll

Benedict Paten

Euan A Ashley

Affiliations

Soon will be listed here.

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 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.

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