Copy Number Studies in Noisy Samples

Microarrays

Philip Ginsbach¹  Bowang Chen²  Yanxiang Jiang¹  Stefan T. Engelter³ 

[1] Neurology Department, University of Heidelberg, INF 400, Heidelberg D69120, Germany; E-Mails:;Division of Molecular Genetic Epidemiology, German Cancer Research Center, INF 280, Heidelberg D69120, Germany; E-Mail:;Stroke Unit and Department of Neurology, University Hospital Basel, Petersgraben 4, Basel CH4031, Switzerland; E-Mail:

关键词: copy number variation (CNV);    variance;    wave noise;    per-SNP noise;    noise-free-cnv software;    noise reduction;    validation of CNV findings;   

DOI  :  10.3390/microarrays2040284

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.