{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:05:51Z","timestamp":1783656351021,"version":"3.55.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["61771381"],"award-info":[{"award-number":["61771381"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["61571341"],"award-info":[{"award-number":["61571341"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>With the rapid development of whole exome sequencing (WES), an increasing number of tools are being proposed for copy number variation (CNV) detection based on this technique. However, no comprehensive guide is available for the use of these tools in clinical settings, which renders them inapplicable in practice. To resolve this problem, in this study, we evaluated the performances of four WES-based CNV tools, and established a guideline for the recommendation of a suitable tool according to the application requirements.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>In this study, first, we selected four WES-based CNV detection tools: CoNIFER, cn.MOPS, CNVkit and exomeCopy. Then, we evaluated their performances in terms of three aspects: sensitivity and specificity, overlapping consistency and computational costs. From this evaluation, we obtained four main results: (1) The sensitivity increases and subsequently stabilizes as the coverage or CNV size increases, while the specificity decreases. (2) CoNIFER performs better for CNV insertions than for CNV deletions, while the remaining tools exhibit the opposite trend. (3) CoNIFER, cn.MOPS and CNVkit realize satisfactory overlapping consistency, which indicates their results are trustworthy. (4) CoNIFER has the best space complexity and cn.MOPS has the best time complexity among these four tools. Finally, we established a guideline for tools\u2019 usage according to these results.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>No available tool performs excellently under all conditions; however, some tools perform excellently in some scenarios. Users can obtain a CNV tool recommendation from our paper according to the targeted CNV size, the CNV type or computational costs of their projects, as presented in Table 1, which is helpful even for users with limited knowledge of computer science.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12859-020-3421-1","type":"journal-article","created":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T16:03:56Z","timestamp":1583424236000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Comparative study of whole exome sequencing-based copy number variation detection tools"],"prefix":"10.1186","volume":"21","author":[{"given":"Lanling","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiguo","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7170-3772","authenticated-orcid":false,"given":"Junbo","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,5]]},"reference":[{"key":"3421_CR1","doi-asserted-by":"publisher","first-page":"S37","DOI":"10.1038\/ng2080","volume":"39","author":"SA Mccarroll","year":"2007","unstructured":"Mccarroll SA. Copy-number variation and association studies of human disease. Nat Genet. 2007;39:S37\u201342.","journal-title":"Nat Genet"},{"issue":"5813","key":"3421_CR2","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1126\/science.1136678","volume":"315","author":"BE Stranger","year":"2007","unstructured":"Stranger BE, Forrest MS, Dunning M, et al. Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science. 2007;315(5813):848\u201353.","journal-title":"Science"},{"issue":"8","key":"3421_CR3","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nrg2593","volume":"10","author":"PJ Hastings","year":"2009","unstructured":"Hastings PJ, Lupski JR, Rosenberg SM, et al. Mechanisms of change in gene copy number. Nat Rev Genet. 2009;10(8):551\u201364.","journal-title":"Nat Rev Genet"},{"key":"3421_CR4","doi-asserted-by":"publisher","unstructured":"Yuan X, Bai J, Zhang J, et al. CONDEL: detecting copy number variation and genotyping deletion Zygosity from single tumor samples using sequence data. IEEE\/ACM Trans Comput Biol Bioinformatics. 2018. https:\/\/doi.org\/10.1109\/TCBB.2018.2883333..","DOI":"10.1109\/TCBB.2018.2883333"},{"issue":"1","key":"3421_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2105-14-150","volume":"14","author":"J Duan","year":"2013","unstructured":"Duan J, Zhang JG, Deng HW, et al. CNV-TV: a robust method to discover copy number variation from short sequencing reads. BMC Bioinformatics. 2013;14(1):1\u201312.","journal-title":"BMC Bioinformatics"},{"issue":"8","key":"3421_CR6","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1101\/gr.3677206","volume":"16","author":"JL Freeman","year":"2006","unstructured":"Freeman JL. Copy number variation: new insights in genome diversity. Genome Res. 2006;16(8):949\u201361.","journal-title":"Genome Res"},{"issue":"1","key":"3421_CR7","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1146\/annurev.genom.8.021307.110233","volume":"8","author":"B Conrad","year":"2007","unstructured":"Conrad B, Antonarakis SE. Gene duplication: a drive for phenotypic diversity and cause of human disease. Annu Rev Genomics Hum Genet. 2007;8(1):17\u201335.","journal-title":"Annu Rev Genomics Hum Genet"},{"issue":"1","key":"3421_CR8","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/1745-6215-15-85","volume":"15","author":"JL Vassy","year":"2014","unstructured":"Vassy JL, Lautenbach DM, Mclaughlin HM, et al. The MedSeq project: a randomized trial of integrating whole genome sequencing into clinical medicine. Trials. 2014;15(1):85.","journal-title":"Trials"},{"issue":"1","key":"3421_CR9","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/ng.499","volume":"42","author":"SB Ng","year":"2009","unstructured":"Ng SB, Buckingham KJ, Lee C, et al. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet. 2009;42(1):30\u20135.","journal-title":"Nat Genet"},{"issue":"11","key":"3421_CR10","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1002\/dneu.22626","volume":"78","author":"S Rohrback","year":"2018","unstructured":"Rohrback S, Siddoway B, Liu CS, et al. Genomic mosaicism in the developing and adult brain. Dev Neurobiol. 2018;78(11):1026\u201348.","journal-title":"Dev Neurobiol"},{"issue":"9","key":"3421_CR11","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1101\/gr.092981.109","volume":"19","author":"S Yoon","year":"2009","unstructured":"Yoon S, Xuan Z, Makarov V, et al. Sensitive and accurate detection of copy number variants using read depth of coverage. Genome Res. 2009;19(9):1586\u201392.","journal-title":"Genome Res"},{"issue":"3","key":"3421_CR12","first-page":"883","volume":"16","author":"L Kadalayil","year":"2014","unstructured":"Kadalayil L, Rafiq S, Rosezerilli MJ, et al. Exome sequence read depth methods for identifying copy number changes. Brief Bioinform. 2014;16(3):883\u20136.","journal-title":"Brief Bioinform"},{"issue":"19","key":"3421_CR13","doi-asserted-by":"publisher","first-page":"2648","DOI":"10.1093\/bioinformatics\/btr462","volume":"27","author":"JF Sathirapongsasuti","year":"2011","unstructured":"Sathirapongsasuti JF, Lee H, Horst BAJ, et al. Exome sequencing-based copy-number variation and loss of heterozygosity detection: ExomeCNV. Bioinformatics. 2011;27(19):2648\u201354.","journal-title":"Bioinformatics."},{"issue":"1","key":"3421_CR14","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1186\/1471-2164-15-661","volume":"15","author":"PS Samarakoon","year":"2014","unstructured":"Samarakoon PS, Sorte HS, et al. Identification of copy number variants from exome sequence data. BMC Genomics. 2014;15(1):661.","journal-title":"BMC Genomics"},{"issue":"1","key":"3421_CR15","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/1471-2105-15-109","volume":"15","author":"H Wang","year":"2014","unstructured":"Wang H, Dan N, Ying K. Copy number variation detection using next generation sequencing read counts. BMC Bioinformatics. 2014;15(1):109.","journal-title":"BMC Bioinformatics"},{"issue":"4","key":"3421_CR16","first-page":"417","volume":"2013","author":"Y Guo","year":"2013","unstructured":"Guo Y, Sheng Q, Samuels DC, et al. Comparative study of exome copy number variation estimation tools using Array comparative genomic hybridization as control. Biomed Res Int. 2013;2013(4):417\u201322.","journal-title":"Biomed Res Int"},{"issue":"8","key":"3421_CR17","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1101\/gr.138115.112","volume":"22","author":"N Krumm","year":"2012","unstructured":"Krumm N, Sudmant PH, Ko A, et al. Copy number variation detection and genotyping from exome sequence data. Genome Res. 2012;22(8):1525\u201332.","journal-title":"Genome Res"},{"issue":"1","key":"3421_CR18","doi-asserted-by":"publisher","first-page":"52","DOI":"10.2202\/1544-6115.1732","volume":"10","author":"MI Love","year":"2011","unstructured":"Love MI, My\u0161i\u010dkov\u00e1 A, Sun R, et al. Modeling read counts for CNV detection in exome sequencing data. Stat Appl Genet Mol Biol. 2011;10(1):52.","journal-title":"Stat Appl Genet Mol Biol"},{"issue":"4","key":"3421_CR19","doi-asserted-by":"publisher","first-page":"e1004873","DOI":"10.1371\/journal.pcbi.1004873","volume":"12","author":"T Eric","year":"2016","unstructured":"Eric T, Hunter SA, Thomas B, et al. CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing. PLoS Comput Biol. 2016;12(4):e1004873.","journal-title":"PLoS Comput Biol"},{"issue":"9","key":"3421_CR20","doi-asserted-by":"publisher","first-page":"e69","DOI":"10.1093\/nar\/gks003","volume":"40","author":"G Klambauer","year":"2012","unstructured":"Klambauer G, Schwarzbauer K, Mayr A, et al. cn.MOPS: mixture of Poissons for discovering copy number variations in next-generation sequencing data with a low false discovery rate. Nucleic Acids Res. 2012;40(9):e69.","journal-title":"Nucleic Acids Res"},{"key":"3421_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/435321","volume":"2013","author":"E. Chatzimichail","year":"2013","unstructured":"Chatzimichail E, Paraskakis E, Rigas A. Predicting Asthma Outcome Using Partial Least Square Regression and Artificial Neural Networks: Hindawi Publishing Corp; 2013. https:\/\/doi.org\/10.1155\/2013\/435321..","journal-title":"Advances in Artificial Intelligence"},{"key":"3421_CR22","first-page":"7","volume":"100","author":"N Watts","year":"2014","unstructured":"Watts N, Rani J, et al. Performance evaluation of improved skew detection and correction using FFT and median filtering. Int J Comput Appl. 2014;100:7\u201316.","journal-title":"Int J Comput Appl"},{"issue":"3","key":"3421_CR23","doi-asserted-by":"publisher","first-page":"e59128","DOI":"10.1371\/journal.pone.0059128","volume":"8","author":"D Junbo","year":"2013","unstructured":"Junbo D, Ji-Gang Z, Hong-Wen D, et al. Comparative Studies of Copy Number Variation Detection Methods for Next-Generation Sequencing Technologies. PLoS One. 2013;8(3):e59128.","journal-title":"PLoS One"},{"issue":"7","key":"3421_CR24","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1002\/humu.22537","volume":"35","author":"R Tan","year":"2014","unstructured":"Tan R, Wang Y, Kleinstein SE, et al. An evaluation of copy number variation detection tools from whole-exome sequencing data. Hum Mutat. 2014;35(7):899\u2013907.","journal-title":"Hum Mutat"},{"issue":"1","key":"3421_CR25","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13039-017-0333-5","volume":"10","author":"R Yao","year":"2017","unstructured":"Yao R, Zhang C, Yu T, et al. Evaluation of three read-depth based CNV detection tools using whole-exome sequencing data. Mol Cytogenet. 2017;10(1):30.","journal-title":"Mol Cytogenet"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-020-3421-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12859-020-3421-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-020-3421-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:12:04Z","timestamp":1614903124000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-020-3421-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,5]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["3421"],"URL":"https:\/\/doi.org\/10.1186\/s12859-020-3421-1","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,5]]},"assertion":[{"value":"8 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"97"}}