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The use of technical replication for detection of low-level somatic mutations in next-generation sequencing.

ABSTRACT: Accurate genome-wide detection of somatic mutations with low variant allele frequency (VAF, <1%) has proven difficult, for which generalized, scalable methods are lacking. Herein, we describe a new computational method, called RePlow, that we developed to detect low-VAF somatic mutations based on simple, library-level replicates for next-generation sequencing on any platform. Through joint analysis of replicates, RePlow is able to remove prevailing background errors in next-generation sequencing analysis, facilitating remarkable improvement in the detection accuracy for low-VAF somatic mutations (up to ~99% reduction in false positives). The method is validated in independent cancer panel and brain tissue sequencing data. Our study suggests a new paradigm with which to exploit an overwhelming abundance of sequencing data for accurate variant detection.

SUBMITTER: Kim J

PROVIDER: S-EPMC6400950 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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The use of technical replication for detection of low-level somatic mutations in next-generation sequencing.

Kim Junho J Kim Dachan D Lim Jae Seok JS Maeng Ju Heon JH Son Hyeonju H Kang Hoon-Chul HC Nam Hojung H Lee Jeong Ho JH Kim Sangwoo S

Nature communications 20190305 1

Accurate genome-wide detection of somatic mutations with low variant allele frequency (VAF, <1%) has proven difficult, for which generalized, scalable methods are lacking. Herein, we describe a new computational method, called RePlow, that we developed to detect low-VAF somatic mutations based on simple, library-level replicates for next-generation sequencing on any platform. Through joint analysis of replicates, RePlow is able to remove prevailing background errors in next-generation sequencing ...[more]

PMID: 30837471

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