PAGE 9 OF 14 Nucleic Acids Research, 2010, Vol. 38, No. 9 e105 Figure 3. Boxplots of ROC curve residual from simulated data for each method. (a) ROC residuals from simulation 1. (b) ROC residuals from simulation 2. Power and false positive rate. For this simulation, all methods but CNVFinder showed similar power to detect predesignated CNVs, with power greater than 99.8% under the NSR optimal parameter setting for each method (Figure 4a; Supplementary Table S4). False positive CNV calls varied greatly from 0 in the QuantiSNP and SNPRank programs to 296 in the CNVFinder program, which translates to a range of false positive rates from 1.65E–5 to 0.006. CNVFinder, GLAD and Nexus Rank had high false positive rates at both the CNV and CNV SNP levels, while CBS had a high rate (0.08) at the CNV level alone (Figure 4b; Supplementary Tables S4 and S6). At the CNV SNP level, ROC residual rankings were diﬀerent primarily due to diﬀerent rankings of false positive rates for the methods. Additionally, the computation of ROC at the CNV SNP level allowed ROC residuals to remain high despite relatively large numbers of false positive CNV SNPs, for example, in CNVFinder. Unlike the analysis of SCORM SNP array data, the total number of CNVs detected by each method displayed minimal variance in this simulated dataset except for the CNVFinder method, which detected the highest number of false positive CNVs under the NSR optimal parameter setting. Failure in CNV detection. Method performance was impaired by simulated CNV size and copy number at parameters that are stricter than NSR optimal. CBS did not detect any three copy CNVs at a strict setting of 5 SD. CNVFinder was impaired in detecting three copy CNVs at stricter settings than optimal. PennCNV had a weakness in detecting the simulated 10-SNP duplication CNVs but not the simulated 20- or 30-SNP CNVs. Nexus Rank and SNPRank had no signiﬁcant failures in detection using the attempted parameters. However, the previous version of these algorithms (4.0) had failures in detecting the simulated 10-SNP CNVs (data not shown). In that version, when a stringent signiﬁcance threshold of 1E–8 was applied, neither Nexus method detected 10-SNP CNVs. The PennCNV method failed to detect 10-SNP CNVs with copy numbers of three or four.