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

Junho Kim, Dachan Kim, Jae Seok Lim, Ju Heon Maeng, Hyeonju Son, Hoon Chul Kang, Hojung Nam, Jeong Ho Lee, Sangwoo Kim

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Article number1047
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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sequencing
mutations
Computational methods
Brain
Genes
Tissue
Mutation
Gene Frequency
Brain Neoplasms
Libraries
genome
Genome
brain
platforms
cancer

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Kim, Junho ; Kim, Dachan ; Lim, Jae Seok ; Maeng, Ju Heon ; Son, Hyeonju ; Kang, Hoon Chul ; Nam, Hojung ; Lee, Jeong Ho ; Kim, Sangwoo. / The use of technical replication for detection of low-level somatic mutations in next-generation sequencing. In: Nature communications. 2019 ; Vol. 10, No. 1.
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The use of technical replication for detection of low-level somatic mutations in next-generation sequencing. / Kim, Junho; Kim, Dachan; Lim, Jae Seok; Maeng, Ju Heon; Son, Hyeonju; Kang, Hoon Chul; Nam, Hojung; Lee, Jeong Ho; Kim, Sangwoo.

In: Nature communications, Vol. 10, No. 1, 1047, 01.12.2019.

Research output: Contribution to journalArticle

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