{"doi":"10.1038/s41587-019-0217-9","title":"Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome","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.","journal":"Nature Biotechnology","year":2019,"id":9008,"datarank":1.133464195416038,"base_score":7.556427969440253,"endowment":7.556427969440253,"self_citation_contribution":1.133464195416038,"citation_network_contribution":0.0,"self_endowment_contribution":1.133464195416038,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1912,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0464,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2019-08-12","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":2120,"name":"Paul Peluso","orcid":"0000-0002-9723-5185","position":1,"is_corresponding":false},{"id":77518,"name":"William J. 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