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Kernel-Based Aggregation of Marker-Level Genetic Association Tests Involving Copy-Number Variation
Microarrays 2013, 2(4), 284-303; doi:10.3390/microarrays2040284

Copy Number Studies in Noisy Samples

1 Neurology Department, University of Heidelberg, INF 400, Heidelberg D69120, Germany 2 Division of Molecular Genetic Epidemiology, German Cancer Research Center, INF 280, Heidelberg D69120, Germany 3 Stroke Unit and Department of Neurology, University Hospital Basel, Petersgraben 4, Basel CH4031, Switzerland These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 20 September 2013 / Revised: 24 October 2013 / Accepted: 25 October 2013 / Published: 6 November 2013
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System noise was analyzed in 77 Affymetrix 6.0 samples from a previous clinical study of copy number variation (CNV). Twenty-three samples were classified as eligible for CNV detection, 29 samples as ineligible and 25 were classified as being of intermediate quality. New software (“noise-free-cnv”) was developed to visualize the data and reduce system noise. Fresh DNA preparations were more likely to yield eligible samples (p < 0.001). Eligible samples had higher rates of successfully genotyped SNPs (p < 0.001) and lower variance of signal intensities (p < 0.001), yielded fewer CNV findings after Birdview analysis (p < 0.001), and showed a tendency to yield fewer PennCNV calls (p = 0.053). The noise-free-cnv software visualized trend patterns of noise in the signal intensities across the ordered SNPs, including a wave pattern of noise, being co-linear with the banding pattern of metaphase chromosomes, as well as system deviations of individual probe sets (per-SNP noise). Wave noise and per-SNP noise occurred independently and could be separately removed from the samples. We recommend a two-step procedure of CNV validation, including noise reduction and visual inspection of all CNV calls, prior to molecular validation of a selected number of putative CNVs.
Keywords: copy number variation (CNV); variance; wave noise; per-SNP noise; noise-free-cnv software; noise reduction; validation of CNV findings copy number variation (CNV); variance; wave noise; per-SNP noise; noise-free-cnv software; noise reduction; validation of CNV findings
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Ginsbach, P.; Chen, B.; Jiang, Y.; Engelter, S.T.; Grond-Ginsbach, C. Copy Number Studies in Noisy Samples. Microarrays 2013, 2, 284-303.

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