Utility of long-read sequencing for All of Us

M. Mahmoud, Y. Huang, K. Garimella, P. A. Audano, W. Wan, N. Prasad, R. E. Handsaker, S. Hall, A. Pionzio, M. C. Schatz, M. E. Talkowski, E. E. Eichler, S. E. Levy and F. J. Sedlazeck ()
Additional contact information
M. Mahmoud: Human Genome Sequencing Center, Baylor College of Medicine
Y. Huang: Broad Institute of MIT and Harvard
K. Garimella: Broad Institute of MIT and Harvard
P. A. Audano: The Jackson Laboratory for Genomic Medicine
W. Wan: Broad Institute of MIT and Harvard
N. Prasad: Discovery Life Sciences
R. E. Handsaker: Harvard Medical School
S. Hall: Discovery Life Sciences
A. Pionzio: Discovery Life Sciences
M. C. Schatz: Johns Hopkins University
M. E. Talkowski: Broad Institute of MIT and Harvard
E. E. Eichler: University of Washington School of Medicine
S. E. Levy: HudsonAlpha Institute for Biotechnology
F. J. Sedlazeck: Human Genome Sequencing Center, Baylor College of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract The All of Us (AoU) initiative aims to sequence the genomes of over one million Americans from diverse ethnic backgrounds to improve personalized medical care. In a recent technical pilot, we compare the performance of traditional short-read sequencing with long-read sequencing in a small cohort of samples from the HapMap project and two AoU control samples representing eight datasets. Our analysis reveals substantial differences in the ability of these technologies to accurately sequence complex medically relevant genes, particularly in terms of gene coverage and pathogenic variant identification. We also consider the advantages and challenges of using low coverage sequencing to increase sample numbers in large cohort analysis. Our results show that HiFi reads produce the most accurate results for both small and large variants. Further, we present a cloud-based pipeline to optimize SNV, indel and SV calling at scale for long-reads analysis. These results lead to widespread improvements across AoU.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-44804-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44804-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-44804-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().