Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome

Published

August 12, 2019

Author(s)

Justin M. Zook, Nathanael D. Olson, Aaron Wenger

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 15 megabases (Mb) and concordance of 99.997%, substantially outperforming assembly with less-accurate long reads.

Citation

Nature Biotechnology

Volume

37

Pub Type

Journals

Download Paper

https://doi.org/10.1038/s41587-019-0217-9

Keywords

human genome, DNA sequencing, genomics

Citation

Zook, J. , Olson, N. and Wenger, A. (2019), Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome, Nature Biotechnology, [online], https://doi.org/10.1038/s41587-019-0217-9 (Accessed October 9, 2025)