Virtual reference signal and noise reduction. A: The raw CN and segmentation results for sample 08_0015 using HapMap as a reference set. Note the absence of the copy number amplification at 43Mb (red dotted oval). B: The raw CN and segmentation results of the average signal computed over the whole tumor data set vs. average signal computed over the HapMap data set. Note the multiple CN events detected (e.g., at 43Mb) due to common CN aberrations in tumor samples. If used as a reference signal, this aberration would cancel out the real CNV in corresponding tumor samples. C: The VN-corrected tumor data set based average signal. Aberrations are removed using the VN algorithm, and the resulting signal can be used as an unbiased reference for further processing. D: The raw CN and segmentation results using the VN based reference signal from C. Note the detection of the copy number amplification (red dotted oval) at 43Mb that would be lost using a HapMap based reference signal.