First Authors | Aaron M Wenger |
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Authors | Aaron M Wenger, Paul Peluso, William J Rowell, Pi-Chuan Chang, Richard J Hall, Gregory T Concepcion, Jana Ebler, Arkarachai Fungtammasan, Alexey Kolesnikov, Nathan D Olson, Armin Töpfer, Michael Alonge, Medhat Mahmoud, Yufeng Qian, Chen-Shan Chin, Adam M Phillippy, Michael C Schatz, Gene Myers, Mark A DePristo, Jue Ruan, Tobias Marschall, Fritz J Sedlazeck, Justin M Zook, Heng Li, Sergey Koren, Andrew Carroll, David R Rank, Michael W Hunkapiller |
Corresponding Authors | |
Last Authors | Michael W Hunkapiller |
Journal Name | Nature biotechnology (Nat Biotechnol) |
Volume | 37 |
Issue | 10 |
Page Range | 1155-1162 |
Open Access | false |
Print Publication Date | 2019-10-01 |
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Abstract | The DNA sequencing technologies in use today produce either highly accurate short reads or less-accurate long reads. We report the optimization of circular consensus sequencing (CCS) to improve the accuracy of single-molecule real-time (SMRT) sequencing (PacBio) and generate highly accurate (99.8%) long high-fidelity (HiFi) reads with an average length of 13.5 kilobases (kb). We applied our approach to sequence the well-characterized human HG002/NA24385 genome and obtained precision and recall rates of at least 99.91% for single-nucleotide variants (SNVs), 95.98% for insertions and deletions <50 bp (indels) and 95.99% for structural variants. Our CCS method matches or exceeds the ability of short-read sequencing to detect small variants and structural variants. We estimate that 2,434 discordances are correctable mistakes in the 'genome in a bottle' (GIAB) benchmark set. Nearly all (99.64%) variants can be phased into haplotypes, further improving variant detection. De novo genome assembly using CCS reads alone produced a contiguous and accurate genome with a contig N50 of >15 megabases (Mb) and concordance of 99.997%, substantially outperforming assembly with less-accurate long reads. |
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Affiliated With | Myers |
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Publication Status | Published |
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DOI | 10.1038/s41587-019-0217-9 |
PubMed ID | 31406327 |
WebOfScience Link | WOS:000493315800017 |
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Display Publisher Download Only | false |
Visible On MPI-CBG Website | true |
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Created By | thuem |
Added Date | 2019-09-18 |
Last Edited By | thuem |
Last Edited Date | 2019-11-22 10:53:09.407 |
Library ID | 7504 |
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Entry Complete | true |
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Include in Edoc Report | true |
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