The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome
Open accessPublished version of a preprint
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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“more than two-thirds of SVs have been missed in studies that used short-read data and the human reference assembly6–8”
From A draft human pangenome reference. (2023) · cites this paper as [7]
Experimental — accuracy not yet measuredIn the citing paper
“Recent technological advances by PacBio have enabled circular consensus sequencing of both RNA and DNA, resulting in long (>10 kb), highly accurate (99.8%) reads (136).”
From Tandem repeats lead to sequence assembly errors and impose multi-level challenges for genome and protein databases (2019) · cites this paper as [136]
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Cites
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Self-citationMinimap2: Pairwise alignment for nucleotide sequences
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Self-citationBUSCO: assessing genome assembly and annotation completeness with single-copy orthologs
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A framework for variation discovery and genotyping using next-generation DNA sequencing data
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Self-citationMerqury: reference-free quality, completeness, and phasing assessment for genome assemblies
Rhie, A., Walenz, B. P., Koren, S., & Phillippy, A. M. (2020) · Genome Biology · doi:10.1186/s13059-020-02134-9 · Cited by 3,643
Self-citationThe complete sequence of a human genome
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Self-citationOpportunities and challenges in long-read sequencing data analysis
Amarasinghe, S. L., Su, S., Dong, X., Zappia, L., Ritchie, M. E., & Gouil, Q. (2020) · Genome Biology · doi:10.1186/s13059-020-1935-5 · Cited by 2,530
MitoHiFi: a python pipeline for mitochondrial genome assembly from PacBio high fidelity reads
Uliano‐Silva, M., Ferreira, J. G. R. N., Krasheninnikova, K., Blaxter, M., Mieszkowska, N., Hall, N., Holland, P. W. H., Durbin, R. M., Richards, T. A., Kersey, P. J., et al. (2023) · BMC Bioinformatics · doi:10.1186/s12859-023-05385-y · Cited by 1,939
Metadata
- Authors
- Wenger, A. M., Peluso, P., Rowell, W. J., Chang, P.-C., Hall, R. J., Concepcion, G. T., Ebler, J., Fungtammasan, A., Kolesnikov, A., Olson, N. D., Töpfer, A., Alonge, M., Mahmoud, M., Qian, Y., Chin, C.-S., Phillippy, A. M., Schatz, M. C., Myers, G., DePristo, M. A., Ruan, J., Marschall, T., Sedlazeck, F. J., Zook, J. M., Li, H., Koren, S., Carroll, A., Rank, D. R., & Hunkapiller, M. W.
- Affiliations
- Pacific Biosciences (United States) (US)
- Google (United States) (US)
- Max Planck Institute for Informatics (DE)
- DNAnexus (United States) (US)
- National Institute of Standards and Technology (US)
- Johns Hopkins University (US)
- Baylor College of Medicine (US)
- National Institutes of Health (US)
- Agricultural Genomics Institute at Shenzhen (CN)
- Dana-Farber Cancer Institute (US)
- Corresponding author
- Rank, David R.
- Hunkapiller, Michael W.
- ORCID
- Wenger, Aaron M.
- Peluso, Paul
- Rowell, William J.
- Chang, Pi-Chuan
- Hall, Richard J.
- Concepcion, Gregory T.
- Ebler, Jana
- Fungtammasan, Arkarachai
- Kolesnikov, Alexey
- Olson, Nathan D.
- Töpfer, Armin
- Alonge, Michael
- Mahmoud, Medhat
- Chin, Chen-Shan
- Phillippy, Adam M.
- Schatz, Michael C.
- DePristo, Mark A.
- Ruan, Jue
- Marschall, Tobias
- Sedlazeck, Fritz J.
- Zook, Justin M.
- Li, Heng
- Koren, Sergey
- Carroll, Andrew
- Rank, David R.
- Hunkapiller, Michael W.
- Venue
- Nature Biotechnology
- Published
- 2019-08-12
- Volume
- 37
- Issue
- 10
- Pages
- 1155-1162
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC6776680
- OpenAlex
- W2968499116
- Cited by
- 1,841
- References
- 57
- Citations by year
- 2026: 246 · 2025: 300 · 2024: 326 · 2023: 275 · 2022: 261 · 2021: 241 · 2020: 133 · 2019: 56
- FWCI
- 60.58
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Biotechnology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (391137747, 395192176)
- National Science Foundation (DBI-1350041)
- U.S. Department of Health & Human Services | National Institutes of Health (R01-HG006677, UM1 HG008898, 1R01HG010040)
- U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute
- National Natural Science Foundation of China (31571353, 31822029)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- circular consensus sequencing, single-molecule real-time sequencing, PacBio HiFi reads, variant calling, structural variants, indels, single nucleotide variants, haplotype phasing, de novo genome assembly
- MeSH terms
- Base Sequence, DNA, Circular, Haplotypes, Humans, Genetic Variation, Genome, Human, Sequence Analysis, DNA, High-Throughput Nucleotide Sequencing
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