{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T02:31:30Z","timestamp":1772245890822,"version":"3.50.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Co-barcoded reads originating from long DNA fragments (mean length &amp;gt;30 kbp) maintain both single base level accuracy and long-range genomic information. We propose a pipeline, stLFRsv, to detect structural variation using co-barcoded reads. stLFRsv identifies abnormal large gaps between co-barcoded reads to detect potential breakpoints and reconstruct complex structural variants (SVs). Haplotype phasing by co-barcoded reads increases the signal to noise ratio, and barcode sharing profiles are used to filter out false positives. We integrate the short read SV caller smoove for smaller variants with stLFRsv. The integrated pipeline was evaluated on the well-characterized genome HG002\/NA24385, and 74.5% precision and a 22.4% recall rate were obtained for deletions. stLFRsv revealed some large variants not included in the benchmark set that were verified by long reads or assembly. For the HG001\/NA12878 genome, stLFRsv also achieved the best performance for both resource usage and the detection of large variants. Our work indicates that co-barcoded read technology has the potential to improve genome completeness.<\/jats:p>","DOI":"10.3389\/fgene.2021.636239","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T01:52:07Z","timestamp":1616032327000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["stLFRsv: A Germline Structural Variant Analysis Pipeline Using Co-barcoded Reads"],"prefix":"10.3389","volume":"12","author":[{"given":"Junfu","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ou","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanming","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongmei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/nrg2958","article-title":"Genome structural variation discovery and genotyping.","volume":"12","author":"Alkan","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.cell.2018.12.019","article-title":"Characterizing the major structural variant alleles of the human genome.","volume":"176","author":"Audano","year":"2019","journal-title":"Cell"},{"key":"B3","author":"Brent","year":"2018","journal-title":"Smoove."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1101\/2020.02.01.930107","article-title":"Fast and accurate assembly of Nanopore reads via progressive error correction and adaptive read selection.","author":"Chen","year":"2020","journal-title":"bioRxiv"},{"key":"B5","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1101\/gr.213462.116","article-title":"HapCUT2: robust and accurate haplotype assembly for diverse sequencing technologies.","volume":"27","author":"Edge","year":"2017","journal-title":"Genome Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1093\/bioinformatics\/btx712","article-title":"Identifying structural variants using linked-read sequencing data.","volume":"34","author":"Elyanow","year":"2018","journal-title":"Bioinformatics"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13397-7","article-title":"LinkedSV for detection of mosaic structural variants from linked-read exome and genome sequencing data.","volume":"10","author":"Fang","year":"2019","journal-title":"Nat. Commun."},{"key":"B8","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/nrg1767","article-title":"Structural variation in the human genome.","volume":"7","author":"Feuk","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/nbt.4060","article-title":"Nanopore sequencing and assembly of a human genome with ultra-long reads.","volume":"36","author":"Jain","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1136\/jmg.2005.036061","article-title":"CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene.","volume":"43","author":"Jongmans","year":"2006","journal-title":"J. Med. Genet."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-6-r84","article-title":"LUMPY: a probabilistic framework for structural variant discovery.","volume":"15","author":"Layer","year":"2014","journal-title":"Genome biol."},{"key":"B12","article-title":"Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM.","author":"Li","year":"2013","journal-title":"arXiv"},{"key":"B13","doi-asserted-by":"publisher","first-page":"3094","DOI":"10.1093\/bioinformatics\/bty191","article-title":"Minimap2: pairwise alignment for nucleotide sequences.","volume":"34","author":"Li","year":"2018","journal-title":"Bioinformatics"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1038\/gim.2016.58","article-title":"Navigating highly homologous genes in a molecular diagnostic setting: a resource for clinical next-generation sequencing.","volume":"18","author":"Mandelker","year":"2016","journal-title":"Genet. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1101\/gr.234443.118","article-title":"Resolving the full spectrum of human genome variation using Linked-Reads.","volume":"29","author":"Marks","year":"2019","journal-title":"Genome Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data.","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1101\/551028","article-title":"Detection and assembly of novel sequence insertions using Linked-Read technology.","author":"Meleshko","year":"2019","journal-title":"bioRxiv"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-5-r52","article-title":"Towards a comprehensive structural variation map of an individual human genome.","volume":"11","author":"Pang","year":"2010","journal-title":"Genome Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/ng1718","article-title":"APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy.","volume":"38","author":"Rovelet-Lecrux","year":"2006","journal-title":"Nat. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1038\/s41592-018-0001-7","article-title":"Accurate detection of complex structural variations using single-molecule sequencing.","volume":"15","author":"Sedlazeck","year":"2018","journal-title":"Nat. Methods"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12065","article-title":"Long-read sequencing and de novo assembly of a Chinese genome.","volume":"7","author":"Shi","year":"2016","journal-title":"Nat. Commun."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090278","article-title":"[alpha]-synuclein locus triplication causes Parkinson\u2019s disease.","volume":"302","author":"Singleton","year":"2003","journal-title":"Science"},{"key":"B23","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/nmeth.4366","article-title":"Genome-wide reconstruction of complex structural variants using read clouds.","volume":"14","author":"Spies","year":"2017","journal-title":"Nat. Methods"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004873","article-title":"CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing.","volume":"12","author":"Talevich","year":"2016","journal-title":"PLoS Comput. Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1109\/IPDPS.2019.00041","article-title":"Efficient architecture-aware acceleration of BWA-MEM for multicore systems","author":"Vasimuddin","year":"2019","journal-title":"2019 IEEE International Parallel and Distributed Processing Symposium (IPDPS)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1101\/gr.245126.118","article-title":"Efficient and unique cobarcoding of second-generation sequencing reads from long DNA molecules enabling cost-effective and accurate sequencing, haplotyping, and de novo assembly.","volume":"29","author":"Wang","year":"2019","journal-title":"Genome Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1038\/s41587-019-0217-9","article-title":"Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome.","volume":"37","author":"Wenger","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1193","article-title":"Identification of large rearrangements in cancer genomes with barcode linked reads.","volume":"46","author":"Xia","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/nbt.3897","article-title":"Haplotype phasing of whole human genomes using bead-based barcode partitioning in a single tube.","volume":"35","author":"Zhang","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/nbt.3432","article-title":"Haplotyping germline and cancer genomes with high-throughput linked-read sequencing.","volume":"34","author":"Zheng","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1101\/660605","article-title":"Aquila: diploid personal genome assembly and comprehensive variant detection based on linked reads.","author":"Zhou","year":"2019","journal-title":"bioRxiv"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1101\/664623","article-title":"A robust benchmark for germline structural variant detection.","author":"Zook","year":"2019","journal-title":"BioRxiv"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.636239\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T01:52:11Z","timestamp":1616032331000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.636239\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,18]]},"references-count":32,"alternative-id":["10.3389\/fgene.2021.636239"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2021.636239","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.06.15.141721","asserted-by":"object"}]},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,18]]},"article-number":"636239"}}