{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:27:39Z","timestamp":1763036859746},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: The detection of structural variations (SVs) in short-range Paired-End (PE) libraries remains challenging because SV breakpoints can involve large dispersed repeated sequences, or carry inherent complexity, hardly resolvable with classical PE sequencing data. In contrast, large insert-size sequencing libraries (Mate-Pair libraries) provide higher physical coverage of the genome and give access to repeat-containing regions. They can thus theoretically overcome previous limitations as they are becoming routinely accessible. Nevertheless, broad insert size distributions and high rates of chimerical sequences are usually associated to this type of libraries, which makes the accurate annotation of SV challenging.<\/jats:p>\n               <jats:p>Results: Here, we present Ulysses, a tool that achieves drastically higher detection accuracy than existing tools, both on simulated and real mate-pair sequencing datasets from the 1000 Human Genome project. Ulysses achieves high specificity over the complete spectrum of variants by assessing, in a principled manner, the statistical significance of each possible variant (duplications, deletions, translocations, insertions and inversions) against an explicit model for the generation of experimental noise. This statistical model proves particularly useful for the detection of low frequency variants. SV detection performed on a large insert Mate-Pair library from a breast cancer sample revealed a high level of somatic duplications in the tumor and, to a lesser extent, in the blood sample as well. Altogether, these results show that Ulysses is a valuable tool for the characterization of somatic mosaicism in human tissues and in cancer genomes.<\/jats:p>\n               <jats:p>Availability and implementation: Ulysses is available at http:\/\/www.lcqb.upmc.fr\/ulysses.<\/jats:p>\n               <jats:p>Contact: \u00a0ingrid.lafontaine@upmc.fr or gilles.fischer@upmc.fr<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btu730","type":"journal-article","created":{"date-parts":[[2014,11,8]],"date-time":"2014-11-08T01:28:35Z","timestamp":1415410115000},"page":"801-808","source":"Crossref","is-referenced-by-count":15,"title":["Ulysses: accurate detection of low-frequency structural variations in large insert-size sequencing libraries"],"prefix":"10.1093","volume":"31","author":[{"given":"Alexandre","family":"Gillet-Markowska","sequence":"first","affiliation":[{"name":"1 Sorbonne Universit\u00e9s, UPMC University Paris 06, UMR 7238, Biologie Computationnelle et Quantitative and 2CNRS, UMR7238, Laboratory of Computational and Quantitative Biology, F-75005 Paris, France"},{"name":"1 Sorbonne Universit\u00e9s, UPMC University Paris 06, UMR 7238, Biologie Computationnelle et Quantitative and 2CNRS, UMR7238, Laboratory of Computational and Quantitative Biology, F-75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugues","family":"Richard","sequence":"additional","affiliation":[{"name":"1 Sorbonne Universit\u00e9s, UPMC University Paris 06, UMR 7238, Biologie Computationnelle et Quantitative and 2CNRS, UMR7238, Laboratory of Computational and Quantitative Biology, F-75005 Paris, France"},{"name":"1 Sorbonne Universit\u00e9s, UPMC University Paris 06, UMR 7238, Biologie Computationnelle et Quantitative and 2CNRS, UMR7238, Laboratory of Computational and Quantitative Biology, F-75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilles","family":"Fischer","sequence":"additional","affiliation":[{"name":"1 Sorbonne Universit\u00e9s, UPMC University Paris 06, UMR 7238, Biologie Computationnelle et Quantitative and 2CNRS, UMR7238, Laboratory of Computational and Quantitative Biology, F-75005 Paris, France"},{"name":"1 Sorbonne Universit\u00e9s, UPMC University Paris 06, UMR 7238, Biologie Computationnelle et Quantitative and 2CNRS, UMR7238, Laboratory of Computational and Quantitative Biology, F-75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Lafontaine","sequence":"additional","affiliation":[{"name":"1 Sorbonne Universit\u00e9s, UPMC University Paris 06, UMR 7238, Biologie Computationnelle et Quantitative and 2CNRS, UMR7238, Laboratory of Computational and Quantitative Biology, F-75005 Paris, France"},{"name":"1 Sorbonne Universit\u00e9s, UPMC University Paris 06, UMR 7238, Biologie Computationnelle et Quantitative and 2CNRS, UMR7238, Laboratory of Computational and Quantitative Biology, F-75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,11,7]]},"reference":[{"key":"2023020116175259400_btu730-B1","first-page":"595","article-title":"AGE: defining breakpoints of genomic structural variants at single-nucleotide resolution, through optimal alignments with gap excision","volume":"27","author":"Abyzov","year":"2011","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023020116175259400_btu730-B2","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/ng.437","article-title":"Personalized copy number and segmental duplication maps using next-generation sequencing","volume":"41","author":"Alkan","year":"2009","journal-title":"Nat. Genet."},{"key":"2023020116175259400_btu730-B3","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/ng.128","article-title":"Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing","volume":"40","author":"Campbell","year":"2008","journal-title":"Nat. Genet."},{"key":"2023020116175259400_btu730-B4","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nmeth.1363","article-title":"Breakdancer: an algorithm for high-resolution mapping of genomic structural variation","volume":"6","author":"Chen","year":"2009","journal-title":"Nat. Methods"},{"key":"2023020116175259400_btu730-B5","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nmeth.1276","article-title":"High-resolution mapping of copy-number alterations with massively parallel sequencing","volume":"6","author":"Chiang","year":"2009","journal-title":"Nat. Methods"},{"key":"2023020116175259400_btu730-B6","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1038\/ng2042","article-title":"The population genetics of structural variation","volume":"39","author":"Conrad","year":"2007","journal-title":"Nat. Genet."},{"key":"2023020116175259400_btu730-B7","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/ng2046","article-title":"Fcgr3b copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity","volume":"39","author":"Fanciulli","year":"2007","journal-title":"Nat. Genet."},{"key":"2023020116175259400_btu730-B8","doi-asserted-by":"crossref","first-page":"e1002334","DOI":"10.1371\/journal.pgen.1002334","article-title":"Relative burden of large CNVs on a range of neurodevelopmental phenotypes","volume":"7","author":"Girirajan","year":"2011","journal-title":"PLoS Genet."},{"key":"2023020116175259400_btu730-B9","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/ng.768","article-title":"Discovery and genotyping of genome structural polymorphism by sequencing on a population scale","volume":"43","author":"Handsaker","year":"2011","journal-title":"Nat. Genet."},{"key":"2023020116175259400_btu730-B10","doi-asserted-by":"crossref","first-page":"e83356","DOI":"10.1371\/journal.pone.0083356","article-title":"SoftSearch: integration of multiple sequence features to identify breakpoints of structural variations","volume":"8","author":"Hart","year":"2013","journal-title":"PLoS One"},{"key":"2023020116175259400_btu730-B11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/ng.2007.48","article-title":"Psoriasis is associated with increased beta-defensin genomic copy number","volume":"40","author":"Hollox","year":"2008","journal-title":"Nat. Genet."},{"key":"2023020116175259400_btu730-B12","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1101\/gr.088633.108","article-title":"Combinatorial algorithms for structural variation detection in high-throughput sequenced genomes","volume":"19","author":"Hormozdiari","year":"2009","journal-title":"Genome Res."},{"key":"2023020116175259400_btu730-B13","first-page":"i350","article-title":"Next-generation VariationHunter: combinatorial algorithms for transposon insertion discovery","volume":"26","author":"Hormozdiari","year":"2010","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023020116175259400_btu730-B14","first-page":"1","article-title":"Systems consequences of amplicon formation in human breast cancer","volume":"11","author":"Inaki","year":"2014","journal-title":"Genome Res."},{"key":"2023020116175259400_btu730-B15","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/ng.2270","article-title":"Detectable clonal mosaicism and its relationship to aging and cancer","volume":"44","author":"Jacobs","year":"2012","journal-title":"Nat. Genet."},{"key":"2023020116175259400_btu730-B16","first-page":"2576","article-title":"PRISM: pair-read informed split-read mapping for base-pair level detection of insertion, deletion and structural variants","volume":"28","author":"Jiang","year":"2012","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023020116175259400_btu730-B17","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature06862","article-title":"Mapping and sequencing of structural variation from eight human genomes","volume":"453","author":"Kidd","year":"2008","journal-title":"Nature"},{"key":"2023020116175259400_btu730-B18","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1126\/science.1149504","article-title":"Paired-end mapping reveals extensive structural variation in the human genome","volume":"318","author":"Korbel","year":"2007","journal-title":"Science"},{"key":"2023020116175259400_btu730-B19","doi-asserted-by":"crossref","first-page":"R23","DOI":"10.1186\/gb-2009-10-2-r23","article-title":"PEMer: a computational framework with simulation-based error models for inferring genomic structural variants from massive paired-end sequencing data","volume":"10","author":"Korbel","year":"2009","journal-title":"Genome Biol."},{"key":"2023020116175259400_btu730-B20","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nbt.1600","article-title":"Nucleotide-resolution analysis of structural variants using BreakSeq and a breakpoint library","volume":"28","author":"Lam","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"2023020116175259400_btu730-B21","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/ng.2271","article-title":"Detectable clonal mosaicism from birth to old age and its relationship to cancer","volume":"44","author":"Laurie","year":"2012","journal-title":"Nat. Genet."},{"key":"2023020116175259400_btu730-B22","doi-asserted-by":"crossref","first-page":"i59","DOI":"10.1093\/bioinformatics\/btn176","article-title":"A robust framework for detecting structural variations in a genome","volume":"24","author":"Lee","year":"2008","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023020116175259400_btu730-B23","first-page":"473","article-title":"MoDIL: detecting small indels from clone-end sequencing with mixtures of distributions","volume":"6","author":"Lee","year":"2009","journal-title":"Nat. Publ. Group"},{"key":"2023020116175259400_btu730-B24","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence alignment\/map format and samtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2023020116175259400_btu730-B25","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1093\/bioinformatics\/bts566","article-title":"Clever: clique-enumerating variant finder","volume":"28","author":"Marschall","year":"2012","journal-title":"Bioinformatics"},{"key":"2023020116175259400_btu730-B26","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1126\/science.1243472","article-title":"Mosaic copy number variation in human neurons","volume":"342","author":"McConnell","year":"2013","journal-title":"Science"},{"key":"2023020116175259400_btu730-B27","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1101\/gr.106344.110","article-title":"Detecting copy number variation with mated short reads","volume":"20","author":"Medvedev","year":"2010","journal-title":"Genome Res."},{"key":"2023020116175259400_btu730-B28","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature09708","article-title":"Mapping copy number variation by population-scale genome sequencing","volume":"470","author":"Mills","year":"2011","journal-title":"Nature"},{"key":"2023020116175259400_btu730-B29","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nature09146","article-title":"Functional impact of global rare copy number variation in autism spectrum disorders","volume":"466","author":"Pinto","year":"2010","journal-title":"Nature"},{"issue":"Web Server issue","key":"2023020116175259400_btu730-B30","doi-asserted-by":"crossref","first-page":"W567","DOI":"10.1093\/nar\/gkr506","article-title":"inGAP-sv: a novel scheme to identify and visualize structural variation from paired end mapping data","volume":"39","author":"Qi","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2023020116175259400_btu730-B31","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1101\/gr.102970.109","article-title":"Genome-wide mapping and assembly of structural variant breakpoints in the mouse genome","volume":"20","author":"Quinlan","year":"2010","journal-title":"Genome Res."},{"key":"2023020116175259400_btu730-B32","doi-asserted-by":"crossref","first-page":"I333","DOI":"10.1093\/bioinformatics\/bts378","article-title":"Delly: structural variant discovery by integrated paired-end and split-read analysis","volume":"28","author":"Rausch","year":"2012","journal-title":"Bioinformatics"},{"key":"2023020116175259400_btu730-B33","first-page":"i222","article-title":"A geometric approach for classification and comparison of structural variants","volume":"25","author":"Sindi","year":"2009","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023020116175259400_btu730-B34","doi-asserted-by":"crossref","first-page":"R22","DOI":"10.1186\/gb-2012-13-3-r22","article-title":"An integrative probabilistic model for identification of structural variation in sequencing data","volume":"13","author":"Sindi","year":"2012","journal-title":"Genome Biol."},{"key":"2023020116175259400_btu730-B35","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.tins.2010.04.001","article-title":"Line-1 retrotransposons: mediators of somatic variation in neuronal genomes?","volume":"33","author":"Singer","year":"2010","journal-title":"Trends Neurosci."},{"key":"2023020116175259400_btu730-B36","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/nature08645","article-title":"Complex landscapes of somatic rearrangement in human breast cancer genomes","volume":"462","author":"Stephens","year":"2009","journal-title":"Nature"},{"key":"2023020116175259400_btu730-B37","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1467-9868.2004.00439.x","article-title":"Strong control, conservative point estimation and simultaneous conservative consistency of false discovery rates: a unified approach","volume":"66","author":"Storey","year":"2004","journal-title":"J. R. Stat. Soc. Ser. B Statist. Methodol."},{"key":"2023020116175259400_btu730-B38","doi-asserted-by":"crossref","first-page":"6119","DOI":"10.1093\/nar\/gkt345","article-title":"Single-cell paired-end genome sequencing reveals structural variation per cell cycle","volume":"41","author":"Voet","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2023020116175259400_btu730-B39","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/nmeth.1628","article-title":"CREST maps somatic structural variation in cancer genomes with base-pair resolution","volume":"8","author":"Wang","year":"2011","journal-title":"Nat. Methods"},{"key":"2023020116175259400_btu730-B40","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.cell.2013.04.010","article-title":"Diverse mechanisms of somatic structural variations in human cancer genomes","volume":"153","author":"Yang","year":"2013","journal-title":"Cell"},{"key":"2023020116175259400_btu730-B41","first-page":"2865","article-title":"Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads","volume":"25","author":"Ye","year":"2009","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023020116175259400_btu730-B42","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1101\/gr.092981.109","article-title":"Sensitive and accurate detection of copy number variants using read depth of coverage","volume":"19","author":"Yoon","year":"2009","journal-title":"Genome Res."},{"key":"2023020116175259400_btu730-B43","first-page":"1895","article-title":"SVDetect: a tool to identify genomic structural variations from paired-end and mate-pair sequencing data","volume":"26","author":"Zeitouni","year":"2010","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023020116175259400_btu730-B44","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1186\/1471-2164-12-375","article-title":"Identification of genomic indels and structural variations using split reads","volume":"12","author":"Zhang","year":"2011","journal-title":"BMC Genomics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/6\/801\/49011403\/bioinformatics_31_6_801.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/6\/801\/49011403\/bioinformatics_31_6_801.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:31:05Z","timestamp":1675297865000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/31\/6\/801\/214659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,7]]},"references-count":44,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,3,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btu730","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2015,3,15]]},"published":{"date-parts":[[2014,11,7]]}}}