Accelerated identification of disease-causing variants with ultra-rapid nanopore genome sequencing.
Journal
Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
23
06
2021
accepted:
13
01
2022
pubmed:
30
3
2022
medline:
20
7
2022
entrez:
29
3
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35347328
doi: 10.1038/s41587-022-01221-5
pii: 10.1038/s41587-022-01221-5
pmc: PMC9287171
doi:
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1035-1041Subventions
Organisme : NHGRI NIH HHS
ID : U01 HG010961
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG010262
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG011853
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG010485
Pays : United States
Organisme : NIH HHS
ID : OT2 OD026682
Pays : United States
Organisme : NHLBI NIH HHS
ID : OT3 HL142481
Pays : United States
Informations de copyright
© 2022. The Author(s).
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