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

Nature Communications
Kaile WangJue Ruan

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.

References

Aug 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Peter J CampbellMichael R Stratton
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Jan 14, 2010·Genome Research·John E PoolRasmus Nielsen
Jan 19, 2010·Nature Methods·Joseph B HiattJay Shendure
Mar 15, 2011·Nature·Nicholas NavinMichael Wigler
May 19, 2011·Proceedings of the National Academy of Sciences of the United States of America·Isaac KindeBert Vogelstein
May 20, 2011·Molecular Ecology Resources·Travis C Glenn
Oct 21, 2011·Nucleic Acids Research·Patrick FlahertyHanlee P Ji
Nov 22, 2011·BMC Bioinformatics·Frazer MeachamLior Pachter
Dec 20, 2011·Nature Biotechnology·Joke ReumersJurgen Del-Favero
Mar 9, 2012·The New England Journal of Medicine·Marco GerlingerCharles Swanton
Apr 24, 2012·Nature Biotechnology·Nicholas J LomanMark J Pallen
May 3, 2012·Nature Communications·Moritz GerstungNiko Beerenwinkel
Aug 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·Michael W SchmittLawrence A Loeb
Feb 12, 2013·Nature Biotechnology·Kristian CibulskisGad Getz
Apr 9, 2013·Nature Biotechnology·Sebastian JünemannDag Harmsen
Nov 19, 2013·Proceedings of the National Academy of Sciences of the United States of America·Dianne I LouSara L Sawyer
Jan 17, 2014·Nature Communications·Niccolo BolliNikhil C Munshi
Apr 4, 2014·Bioinformatics·Anthony M BolgerBjoern Usadel
Jun 27, 2014·Nature Protocols·Ashley Acevedo, Raul Andino
Oct 10, 2014·Nature Protocols·Scott R KennedyLawrence A Loeb
Apr 8, 2015·Nature Methods·Michael W SchmittLawrence A Loeb
Nov 13, 2015·Proceedings of the National Academy of Sciences of the United States of America·Shaoping LingChung-I Wu
Jan 29, 2016·BMC Genomics·Chunfang Zheng, David Sankoff

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Citations

Sep 11, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Ping HuMaximilian Muenke
Mar 21, 2019·Clinical Genetics·Xiaoling YangYuehua Zhang
May 28, 2019·Nucleic Acids Research·Ting Ting WangScott V Bratman
Jun 28, 2018·Cancer Chemotherapy and Pharmacology·Chengliang HuangHong Fan
Nov 5, 2020·PLoS Pathogens·Maoz GelbartAdi Stern
Jun 27, 2021·Trends in Parasitology·Aliou Dia, Ian H Cheeseman
Aug 23, 2021·Journal of Molecular Biology·Paulius MielinisArvydas Lubys
May 12, 2018·Virus Research·Bashar IbrahimManja Marz

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Datasets Mentioned

BETA
PRJNA339672

Methods Mentioned

BETA
PCR
Cir-seq
amplicon sequencing
Duplex-seq
Assay
Genotyping
AmpliSeq

Software Mentioned

NGS
sam2sites
BWA
GATK FisherStrand
RainDrop Analyst
Varscan
o2n
Droplet
SAMtools
Trimmomatic

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