{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T19:11:09Z","timestamp":1774120269589,"version":"3.50.1"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Comparing genomes of individual organisms using next-generation sequencing data is, until now, mostly performed using a reference genome. This is challenging when the reference is distant and introduces bias towards the exact sequence present in the reference. Recent improvements in both sequencing read length and efficiency of assembly algorithms have brought direct comparison of individual genomes by de novo assembly, rather than through a reference genome, within reach.<\/jats:p>\n               <jats:p>Results: Here, we develop and test an algorithm, named Magnolya, that uses a Poisson mixture model for copy number estimation of contigs assembled from sequencing data. We combine this with co-assembly to allow de novo detection of copy number variation (CNV) between two individual genomes, without mapping reads to a reference genome. In co-assembly, multiple sequencing samples are combined, generating a single contig graph with different traversal counts for the nodes and edges between the samples. In the resulting \u2018coloured\u2019 graph, the contigs have integer copy numbers; this negates the need to segment genomic regions based on depth of coverage, as required for mapping-based detection methods. Magnolya is then used to assign integer copy numbers to contigs, after which CNV probabilities are easily inferred. The copy number estimator and CNV detector perform well on simulated data. Application of the algorithms to hybrid yeast genomes showed allotriploid content from different origin in the wine yeast Y12, and extensive CNV in aneuploid brewing yeast genomes. Integer CNV was also accurately detected in a short-term laboratory-evolved yeast strain.<\/jats:p>\n               <jats:p>Availability: Magnolya is implemented in Python and available at: http:\/\/bioinformatics.tudelft.nl\/<\/jats:p>\n               <jats:p>Contact: \u00a0d.deridder@tudelft.nl<\/jats:p>\n               <jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts601","type":"journal-article","created":{"date-parts":[[2012,10,10]],"date-time":"2012-10-10T08:45:27Z","timestamp":1349858727000},"page":"3195-3202","source":"Crossref","is-referenced-by-count":72,"title":["<i>De novo<\/i> detection of copy number variation by co-assembly"],"prefix":"10.1093","volume":"28","author":[{"given":"Jurgen F.","family":"Nijkamp","sequence":"first","affiliation":[{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"},{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"},{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"}]},{"given":"Marcel A.","family":"van den Broek","sequence":"additional","affiliation":[{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"},{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"}]},{"given":"Jan-Maarten A.","family":"Geertman","sequence":"additional","affiliation":[{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"}]},{"given":"Marcel J. T.","family":"Reinders","sequence":"additional","affiliation":[{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"},{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"},{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"}]},{"given":"Jean-Marc G.","family":"Daran","sequence":"additional","affiliation":[{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"},{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"}]},{"given":"Dick","family":"de Ridder","sequence":"additional","affiliation":[{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"},{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"},{"name":"1 The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, 2628 CD Delft, 2Department of Biotechnology, Delft University of Technology, 2628 BC Delft, 3Kluyver Centre for Genomics of Industrial Fermentation, 2600 GA Delft, 4Heineken Supply Chain, Global Research & Development, 2382 PH Zoeterwoude and 5Netherlands Bioinformatics Centre, 6500 HB Nijmegen, The Netherlands"}]}],"member":"286","published-online":{"date-parts":[[2012,10,9]]},"reference":[{"key":"2023012513253819600_bts601-B1","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1093\/bioinformatics\/btr670","article-title":"Control-FREEC: a tool for assessing copy number and allelic content using next-generation sequencing 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and their identification as ADY2 alleles by whole-genome resequencing and transcriptome analysis","volume":"12","author":"de Kok","year":"2012","journal-title":"FEMS Yeast Res."},{"key":"2023012513253819600_bts601-B5","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1093\/nar\/30.11.2478","article-title":"Fast algorithms for large-scale genome alignment and comparison","volume":"30","author":"Delcher","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2023012513253819600_bts601-B6","doi-asserted-by":"crossref","first-page":"546, 563","DOI":"10.1126\/science.274.5287.546","article-title":"Life with 6000 genes","volume":"274","author":"Goffeau","year":"1996","journal-title":"Science"},{"key":"2023012513253819600_bts601-B7","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/ng.1028","article-title":"De novo assembly and genotyping of variants using colored de bruijn graphs","volume":"44","author":"Iqbal","year":"2012","journal-title":"Nat. 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