Ultrasensitive and high-efficiency screen of de novo low-frequency mutations by o2n-seq

Kaile Wang, Shujuan Lai, Xiaoxu Yang, Tianqi Zhu, Xuemei Lu, Chung I. Wu, Jue Ruan

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Detection of de novo, low-frequency mutations is essential for characterizing cancer genomes and heterogeneous cell populations. However, the screening capacity of current ultrasensitive NGS methods is inadequate owing to either low-efficiency read utilization or severe amplification bias. Here, we present O2n-seq, an ultrasensitive and high-efficiency NGS library preparation method for discovering de novo, low-frequency mutations. O2n-seq reduces the error rate of NGS to 10-5-10-8. The efficiency of its data usage is about 10-30 times higher than that of barcode-based strategies. For detecting mutations with allele frequency (AF) 1% in 4.6 Mb-sized genome, the sensitivity and specificity of O2n-seq reach to 99% and 98.64%, respectively. For mutations with AF around 0.07% in phix174, o2n-seq detects all the mutations with 100% specificity. Moreover, we successfully apply o2n-seq to screen de novo, low-frequency mutations in human tumours. O2n-seq will aid to characterize the landscape of somatic mutations in research and clinical settings.

Original languageEnglish (US)
Article number15335
JournalNature communications
Volume8
DOIs
StatePublished - May 22 2017
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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