Calibration-free NGS quantitation of mutations below 0.01% VAF
Peng Dai,
Lucia Ruojia Wu,
Sherry Xi Chen,
Michael Xiangjiang Wang,
Lauren Yuxuan Cheng,
Jinny Xuemeng Zhang,
Pengying Hao,
Weijie Yao,
Jabra Zarka,
Ghayas C. Issa,
Lawrence Kwong and
David Yu Zhang ()
Additional contact information
Peng Dai: Rice University
Lucia Ruojia Wu: Rice University
Sherry Xi Chen: Rice University
Michael Xiangjiang Wang: Rice University
Lauren Yuxuan Cheng: Rice University
Jinny Xuemeng Zhang: NuProbe USA
Pengying Hao: NuProbe USA
Weijie Yao: NuProbe USA
Jabra Zarka: The University of Texas MD Anderson Cancer Center
Ghayas C. Issa: The University of Texas MD Anderson Cancer Center
Lawrence Kwong: The University of Texas MD Anderson Cancer Center
David Yu Zhang: Rice University
Nature Communications, 2021, vol. 12, issue 1, 1-9
Abstract:
Abstract Quantitation of rare somatic mutations is essential for basic research and translational clinical applications including minimal residual disease (MRD) detection. Though unique molecular identifier (UMI) has suppressed errors for rare mutation detection, the sequencing depth requirement is high. Here, we present Quantitative Blocker Displacement Amplification (QBDA) which integrates sequence-selective variant enrichment into UMI quantitation for accurate quantitation of mutations below 0.01% VAF at only 23,000X depth. Using a panel of 20 genes recurrently altered in acute myeloid leukemia, we demonstrate quantitation of various mutations including single base substitutions and indels down to 0.001% VAF at a single locus with less than 4 million sequencing reads, allowing sensitive MRD detection in patients during complete remission. In a pan-cancer panel and a melanoma hotspot panel, we detect mutations down to 0.1% VAF using only 1 million reads. QBDA provides a convenient and versatile method for sensitive mutation quantitation using low-depth sequencing.
Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26308-6
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DOI: 10.1038/s41467-021-26308-6
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