한빛사논문
- 조회709
Jin H. Bae 1,9, Ruolin Liu 1,9, Eugenia Roberts1, Erica Nguyen1, Shervin Tabrizi 1,2,3, Justin Rhoades1, Timothy Blewett1, Kan Xiong1, Gregory Gydush1, Douglas Shea1, Zhenyi An1, Sahil Patel1,2,3, Ju Cheng1, Sainetra Sridhar1, Mei Hong Liu4, Emilie Lassen 5, Anne-Bine Skytte 5, Marta Grońska-Pęski 4, Jonathan E. Shoag6, Gilad D. Evrony4, Heather A. Parsons 7, Erica L. Mayer7, G. Mike Makrigiorgos7, Todd R. Golub 1,7,8 & Viktor A. Adalsteinsson 1
1Broad Institute of MIT and Harvard, Cambridge, MA, USA.
2Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.
3Massachusetts General Hospital, Boston, MA, USA.
4Center for Human Genetics and Genomics, Departments of Pediatrics and Neuroscience & Physiology, New York University Grossman School of Medicine, New York City, NY, USA.
5Cryos International, Aarhus, Denmark.
6University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center, Cleveland, OH, USA.
7Dana-Farber Cancer Institute, Boston, MA, USA.
8Harvard Medical School, Boston, MA, USA.
9These authors contributed equally: Jin H. Bae, Ruolin Liu.
Corresponding author : Correspondence to Viktor A. Adalsteinsson.
Abstract
Detecting mutations from single DNA molecules is crucial in many fields but challenging. Next-generation sequencing (NGS) affords tremendous throughput but cannot directly sequence double-stranded DNA molecules ('single duplexes') to discern the true mutations on both strands. Here we present Concatenating Original Duplex for Error Correction (CODEC), which confers single duplex resolution to NGS. CODEC affords 1,000-fold higher accuracy than NGS, using up to 100-fold fewer reads than duplex sequencing. CODEC revealed mutation frequencies of 2.72 × 10-8 in sperm of a 39-year-old individual, and somatic mutations acquired with age in blood cells. CODEC detected genome-wide, clonal hematopoiesis mutations from single DNA molecules, single mutated duplexes from tumor genomes and liquid biopsies, microsatellite instability with 10-fold greater sensitivity and mutational signatures, and specific tumor mutations with up to 100-fold fewer reads. CODEC enables more precise genetic testing and reveals biologically significant mutations, which are commonly obscured by NGS errors.
논문정보
- Research article
- 2023년 04월 (BRIC 등록일 2023-05-04)
- 국외 연구진
- 생명과학 > 유전학
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