Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Statistical Applications in Genetics and Molecular Biology

Editor-in-Chief: Sanguinetti, Guido

6 Issues per year


IMPACT FACTOR 2017: 0.812
5-year IMPACT FACTOR: 1.104

CiteScore 2017: 0.86

SCImago Journal Rank (SJR) 2017: 0.456
Source Normalized Impact per Paper (SNIP) 2017: 0.527

Mathematical Citation Quotient (MCQ) 2017: 0.04

Online
ISSN
1544-6115
See all formats and pricing
More options …
Volume 17, Issue 2

Issues

Volume 10 (2011)

Volume 9 (2010)

Volume 6 (2007)

Volume 5 (2006)

Volume 4 (2005)

Volume 2 (2003)

Volume 1 (2002)

Noise-robust assessment of SNP array based CNV calls through local noise estimation of log R ratios

Nele CosemansORCID iD: http://orcid.org/0000-0002-9015-2803 / Peter Claes
  • Medical Image Computing, ESAT/PSI, Department of Electrical Engineering, KU Leuven, Leuven, Belgium
  • Medical Imaging Research Center, UZ Leuven, Leuven, Belgium
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Nathalie Brison / Joris Robert Vermeesch / Hilde Peeters
Published Online: 2018-04-28 | DOI: https://doi.org/10.1515/sagmb-2017-0026

Abstract

Arrays based on single nucleotide polymorphisms (SNPs) have been successful for the large scale discovery of copy number variants (CNVs). However, current CNV calling algorithms still have limitations in detecting CNVs with high specificity and sensitivity, especially in case of small (<100 kb) CNVs. Therefore, this study presents a simple statistical analysis to evaluate CNV calls from SNP arrays in order to improve the noise-robustness of existing CNV calling algorithms. The proposed approach estimates local noise of log R ratios and returns the probability that a certain observation is different from this log R ratio noise level. This probability can be triggered at different thresholds to tailor specificity and/or sensitivity in a flexible way. Moreover, a comparison based on qPCR experiments showed that the proposed noise-robust CNV calls outperformed original ones for multiple threshold values.

Keywords: CNV call; copy number variant; local noise estimation; log R ratio; SNP array

References

  • Alkan, C., B. P. Coe and E. E. Eichler (2011): “Genome structural variation discovery and genotyping,” Nat. Rev. Genet., 12, 363–376.CrossrefPubMedGoogle Scholar

  • Asadollahi, R., B. Oneda, P. Joset, S. Azzarello-Burri, D. Bartholdi, K. Steindl, M. Vincent, J. Cobilanschi, H. Sticht, R. Baldinger, R. Reissmann, I. Sudholt, C. T. Thiel, A. B. Ekici, A. Reis, E. K. Bijlsma, J. Andrieux, A. Dieux, D. FitzPatrick, S. Ritter, A. Baumer, B. Latal, B. Plecko, O. G. Jenni and A. Rauch (2014): “The clinical significance of small copy number variants in neurodevelopmental disorders,” J. Med. Genet., 51, 677–688.PubMedWeb of ScienceCrossrefGoogle Scholar

  • Baross, A., A. D. Delaney, H. I. Li, T. Nayar, S. Flibotte, H. Qian, S. Y. Chan, J. Asano, A. Ally, M. Cao, P. Birch, M. Brown-John, N. Fernandes, A. Go, G. Kennedy, S. Langlois, P. Eydoux, J. M. Friedman and M. A. Marra (2007): “Assessment of algorithms for high throughput detection of genomic copy number variation in oligonucleotide microarray data,” BMC Bioinformatics, 8, 368.PubMedWeb of ScienceGoogle Scholar

  • Beckmann, J. S., X. Estivill and S. E. Antonarakis (2007): “Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability,” Nat. Rev. Genet., 8, 639–646.Web of ScienceCrossrefPubMedGoogle Scholar

  • Brady, P. D. and J. R. Vermeesch (2012): “Genomic microarrays: a technology overview,” Prenat. Diagn., 32, 336–343.Web of SciencePubMedCrossrefGoogle Scholar

  • Claes, P., K. Daniels, M. Walters, J. Clement, D. Vandermeulen and P. Suetens (2012): “Dysmorphometrics: the modelling of morphological abnormalities,” Theor. Biol. Med. Model., 9, 5.PubMedCrossrefGoogle Scholar

  • Conrad, D. F., D. Pinto, R. Redon, L. Feuk, O. Gokcumen, Y. Zhang, J. Aerts, T. D. Andrews, C. Barnes, P. Campbell, T. Fitzgerald, M. Hu, C. H. Ihm, K. Kristiansson, D. G. MacArthur, J. R. MacDonald, I. Onyiah, A. W. C. Pang, S. Robson, K. Stirrups, A. Valsesia, K. Walter, J. Wei, C. Tyler-Smith, N. P. Carter, C. Lee, S. W. Scherer and M. E. Hurles (2010): “Origins and functional impact of copy number variation in the human genome,” Nature, 464, 704–712.PubMedCrossrefWeb of ScienceGoogle Scholar

  • Dellinger, A. E., S. M. Saw, L. K. Goh, M. Seielstad, T. L. Young and Y. J. Li (2010): “Comparative analyses of seven algorithms for copy number variant identification from single nucleotide polymorphism arrays,” Nucleic Acids Res., 38, 1–14.Web of ScienceGoogle Scholar

  • Dhami, P., A. J. Coffey, S. Abbs, J. R. Vermeesch, J. P. Dumanski, K. J. Woodward, R. M. Andrews, C. Langford and D. Vetrie (2005): “Exon array CGH: detection of copy-number changes at the resolution of individual exons in the human genome,” Am. J. Hum. Genet., 76, 750–762.PubMedCrossrefGoogle Scholar

  • Eckel-Passow, J. E., E. J. Atkinson, S. Maharjan, S. L. Kardia and M. de Andrade (2011): “Software comparison for evaluating genomic copy number variation for Affymetrix 6.0 SNP array platform,” BMC Bioinformatics, 12, 220.PubMedWeb of ScienceGoogle Scholar

  • Fernandez-Jimenez, N., A. Castellanos-Rubio, L. Plaza-Izurieta, G. Gutierrez, I. Irastorza, L. Castaño, J. C. Vitoria and J. R. Bilbao (2011): “Accuracy in copy number calling by qPCR and PRT: a matter of DNA,” PLoS One, 6, e28910.Web of SciencePubMedGoogle Scholar

  • Ionita-Laza, I., A. J. Rogers, C. Lange, B. A. Raby and C. Lee (2009): “Genetic association analysis of copy-number variation (CNV) in human disease pathogenesis,” Genomics, 93, 22–26.CrossrefPubMedWeb of ScienceGoogle Scholar

  • Jiang, L., J. Jiang, J. Yang, X. Liu, J. Wang, H. Wang, X. Ding, J. Liu and Q. Zhang (2013): “Genome-wide detection of copy number variations using high-density SNP genotyping platforms in Holsteins,” BMC Genomics, 14, 131.PubMedWeb of ScienceGoogle Scholar

  • Karimpour-Fard, A., L. Dumas, T. Phang, J. M. Sikela and L. E. Hunter (2010): “A survey of analysis software for array-comparative genomic hybridisation studies to detect copy number variation,” Hum. Genomics, 4, 421.CrossrefPubMedGoogle Scholar

  • Kirov, G., A. J. Pocklington, P. Holmans, D. Ivanov, M. Ikeda, D. Ruderfer, J. Moran, K. Chambert, D. Toncheva, L. Georgieva, D. Grozeva, M. Fjodorova, R. Wollerton, E. Rees, I. Nikolov, L. N. van de Lagemaat, A. Bayés, E. Fernandez, P. I. Olason, Y. Böttcher, N. H. Komiyama, M. O. Collins, J. Choudhary, K. Stefansson, H. Stefansson, S. G. N. Grant, S. Purcell, P. Sklar, M. C. O’Donovan and M. J. Owen (2012): “De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia,” Mol. Psychiatry, 17, 142–153.Web of ScienceCrossrefPubMedGoogle Scholar

  • Krumm, N., B. J. O’Roak, E. Karakoc, K. Mohajeri, B. Nelson, L. Vives, S. Jacquemont, J. Munson, R. Bernier and E. E. Eichler (2013): “Transmission disequilibrium of small CNVs in simplex autism,” Am. J. Hum. Genet., 93, 595–606.PubMedWeb of ScienceCrossrefGoogle Scholar

  • Macé, A., M. A. Tuke, J. S. Beckmann, L. Lin, S. Jacquemont, M. N. Weedon, A. Reymond and Z. Kutalik (2016): “New quality measure for SNP array based CNV detection,” Bioinformatics, 32, 3298–3305.CrossrefWeb of SciencePubMedGoogle Scholar

  • Marmarelis, V. Z. (2004): Nonlinear dynamic modeling of physiological systems. John Wiley & Sons.Google Scholar

  • McCarthy, S. E., V. Makarov, G. Kirov, A. M. Addington, J. McClellan, S. Yoon, D. O. Perkins, D. E. Dickel, M. Kusenda, O. Krastoshevsky, V. Krause, R. A. Kumar, D. Grozeva, D. Malhotra, T. Walsh, E. H. Zackai, P. Kaplan, J. Ganesh, I. D. Krantz, N. B. Spinner, P. Roccanova, A. Bhandari, K. Pavon, B. Lakshmi, A. Leotta, J. Kendall, Y.-H. Lee, V. Vacic, S. Gary, L. M. Iakoucheva, T. J. Crow, S. L. Christian, J. A. Lieberman, T. S. Stroup, T. Lehtimäki, K. Puura, C. Haldeman-Englert, J. Pearl, M. Goodell, V. L. Willour, P. DeRosse, J. Steele, L. Kassem, J. Wolff, N. Chitkara, F. J. McMahon, A. K. Malhotra, J. B. Potash, T. G. Schulze, M. M. Nöthen, S. Cichon, M. Rietschel, E. Leibenluft, V. Kustanovich, C. M. Lajonchere, J. S. Sutcliffe, D. Skuse, M. Gill, L. Gallagher, N. R. Mendell, N. Craddock, M. J. Owen, M. C. O’Donovan, T. H. Shaikh, E. Susser, L. E. DeLisi, P. F. Sullivan, C. K. Deutsch, J. Rapoport, D. L. Levy, M.-C. King and J. Sebat (2009): “Microduplications of 16p11.2 are associated with schizophrenia,” Nat. Genet., 41, 1223–1227.PubMedCrossrefWeb of ScienceGoogle Scholar

  • Menten, B., N. Maas, B. Thienpont, K. Buysse, J. Vandesompele, C. Melotte, T. de Ravel, S. Van Vooren, I. Balikova, L. Backx, S. Janssens, A. De Paepe, B. De Moor, Y. Moreau, P. Marynen, J.-P. Fryns, G. Mortier, K. Devriendt, F. Speleman and J. R. Vermeesch (2006): “Emerging patterns of cryptic chromosomal imbalance in patients with idiopathic mental retardation and multiple congenital anomalies: a new series of 140 patients and review of published reports,” J. Med. Genet., 43, 625–633.CrossrefPubMedGoogle Scholar

  • Pinto, D., K. Darvishi, X. Shi, D. Rajan, D. Rigler, T. Fitzgerald, A. C. Lionel, B. Thiruvahindrapuram, J. R. Macdonald, R. Mills, A. Prasad, K. Noonan, S. Gribble, E. Prigmore, P. K. Donahoe, R. S. Smith, J. H. Park, M. E. Hurles, N. P. Carter, C. Lee, S. W. Scherer and L. Feuk (2011): “Comprehensive assessment of array-based platforms and calling algorithms for detection of copy number variants,” Nat. Biotechnol., 29, 512–20.PubMedCrossrefWeb of ScienceGoogle Scholar

  • Pinto, D., A. T. Pagnamenta, L. Klei, R. Anney, D. Merico, R. Regan, J. Conroy, T. R. Magalhaes, C. Correia, B. S. Abrahams, J. Almeida, E. Bacchelli, G. D. Bader, A. J. Bailey, G. Baird, A. Battaglia, T. Berney, N. Bolshakova, S. Bölte, P. F. Bolton, T. Bourgeron, S. Brennan, J. Brian, S. E. Bryson, A. R. Carson, G. Casallo, J. Casey, B. H. Y. Chung, L. Cochrane, C. Corsello, E. L. Crawford, A. Crossett, C. Cytrynbaum, G. Dawson, M. de Jonge, R. Delorme, I. Drmic, E. Duketis, F. Duque, A. Estes, P. Farrar, B. A. Fernandez, S. E. Folstein, E. Fombonne, C. M. Freitag, J. Gilbert, C. Gillberg, J. T. Glessner, J. Goldberg, A. Green, J. Green, S. J. Guter, H. Hakonarson, E. A. Heron, M. Hill, R. Holt, J. L. Howe, G. Hughes, V. Hus, R. Igliozzi, C. Kim, S. M. Klauck, A. Kolevzon, O. Korvatska, V. Kustanovich, C. M. Lajonchere, J. A. Lamb, M. Laskawiec, M. Leboyer, A. Le Couteur, B. L. Leventhal, A. C. Lionel, X.-Q. Liu, C. Lord, L. Lotspeich, S. C. Lund, E. Maestrini, W. Mahoney, C. Mantoulan, C. R. Marshall, H. McConachie, C. J. McDougle, J. McGrath, W. M. McMahon, A. Merikangas, O. Migita, N. J. Minshew, G. K. Mirza, J. Munson, S. F. Nelson, C. Noakes, A. Noor, G. Nygren, G. Oliveira, K. Papanikolaou, J. R. Parr, B. Parrini, T. Paton, A. Pickles, M. Pilorge, J. Piven, C. P. Ponting, D. J. Posey, A. Poustka, F. Poustka, A. Prasad, J. Ragoussis, K. Renshaw, J. Rickaby, W. Roberts, K. Roeder, B. Roge, M. L. Rutter, L. J. Bierut, J. P. Rice, J. Salt, K. Sansom, D. Sato, R. Segurado, A. F. Sequeira, L. Senman, N. Shah, V. C. Sheffield, L. Soorya, I. Sousa, O. Stein, N. Sykes, V. Stoppioni, C. Strawbridge, R. Tancredi, K. Tansey, B. Thiruvahindrapduram, A. P. Thompson, S. Thomson, A. Tryfon, J. Tsiantis, H. Van Engeland, J. B. Vincent, F. Volkmar, S. Wallace, K. Wang, Z. Wang, T. H. Wassink, C. Webber, R. Weksberg, K. Wing, K. Wittemeyer, S. Wood, J. Wu, B. L. Yaspan, D. Zurawiecki, L. Zwaigenbaum, J. D. Buxbaum, R. M. Cantor, E. H. Cook, H. Coon, M. L. Cuccaro, B. Devlin, S. Ennis, L. Gallagher, D. H. Geschwind, M. Gill, J. L. Haines, J. Hallmayer, J. Miller, A. P. Monaco, J. I. Nurnberger, A. D. Paterson, M. A. Pericak-Vance, G. D. Schellenberg, P. Szatmari, A. M. Vicente, V. J. Vieland, E. M. Wijsman, S. W. Scherer, J. S. Sutcliffe and C. Betancur (2010): “Functional impact of global rare copy number variation in autism spectrum disorders,” Nature, 466, 368–72.Web of SciencePubMedCrossrefGoogle Scholar

  • Poultney, C. S., A. P. Goldberg, E. Drapeau, Y. Kou, H. Harony-Nicolas, Y. Kajiwara, S. De Rubeis, S. Durand, C. Stevens, K. Rehnström, A. Palotie, M. J. Daly, A. Ma’ayan, M. Fromer and J. D. Buxbaum (2013): “Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder,” Am. J. Hum. Genet., 93, 607–619.CrossrefPubMedWeb of ScienceGoogle Scholar

  • Qi, Y., X. Zhou, D. Bu, P. Hou, J. Lv and H. Zhang (2016): “Comparison of multiple methods for determination of FCGR3A/B genomic copy numbers in HapMap Asian Populations with two public databases,” Front. Genet., 7, 1–7.Web of ScienceGoogle Scholar

  • Robin, X., N. Turck, A. Hainard, N. Tiberti, F. Lisacek, J.-C. Sanchez and M. Müller (2011): “pROC: an open-source package for R and S+ to analyze and compare ROC curves,” BMC Bioinformatics, 12, 77.Web of ScienceCrossrefGoogle Scholar

  • Seiser, E. L. and F. Innocenti (2015): “Hidden Markov model-based CNV detection algorithms for Illumina genotyping microarrays,” Cancer Inform., 13, 77.PubMedGoogle Scholar

  • Valsesia, A., A. Macé, S. Jacquemont, J. S. Beckmann and Z. Kutalik (2013): “The growing importance of CNVs: new insights for detection and clinical interpretation,” Front. Genet., 4, 1–19.Google Scholar

  • Vandeweyer, G., E. Reyniers, W. Wuyts, L. Rooms and R. F. Kooy (2011): “CNV-WebStore: online CNV analysis, storage and interpretation,” BMC Bioinformatics, 12, 4.PubMedWeb of ScienceGoogle Scholar

  • Vermeesch, J. R., P. D. Brady, D. Sanlaville, K. Kok and R. J. Hastings (2012): “Genome-wide arrays: quality criteria and platforms to be used in routine diagnostics,” Hum. Mutat., 33, 906–915.CrossrefWeb of SciencePubMedGoogle Scholar

  • Vermeesch, J. R., H. Fiegler, N. de Leeuw, K. Szuhai, J. Schoumans, R. Ciccone, F. Speleman, A. Rauch, J. Clayton-Smith, C. Van Ravenswaaij, D. Sanlaville, P. C. Patsalis, H. Firth, K. Devriendt and O. Zuffardi (2007): “Guidelines for molecular karyotyping in constitutional genetic diagnosis,” Eur. J. Hum. Genet., 15, 1105–1114.PubMedWeb of ScienceCrossrefGoogle Scholar

  • Winchester, L., C. Yau and J. Ragoussis (2009): “Comparing CNV detection methods for SNP arrays,” Brief. Funct. Genomic. Proteomic., 8, 353–366.PubMedCrossrefGoogle Scholar

  • Zhao, M., Q. Wang, Q. Wang, P. Jia and Z. Zhao (2013): “Computational tools for copy number variation (CNV) detection using next-generation sequencing data: features and perspectives,” BMC Bioinformatics, 14, S1.PubMedWeb of ScienceGoogle Scholar

About the article

Published Online: 2018-04-28


Citation Information: Statistical Applications in Genetics and Molecular Biology, Volume 17, Issue 2, 20170026, ISSN (Online) 1544-6115, DOI: https://doi.org/10.1515/sagmb-2017-0026.

Export Citation

©2018 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Comments (0)

Please log in or register to comment.
Log in