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Mass spectrometry is being used to find disease-related patterns in mixtures of proteins derived from biological fluids. Questions have been raised about the reproducibility and reliability of peak quantifications using this technology. We collected nipple aspirate fluid from breast cancer patients and healthy women, pooled them into a quality control sample, and produced 24 replicate SELDI spectra. We developed a novel algorithm to process the spectra, denoising with the undecimated discrete wavelet transform (UDWT), and evaluated it for consistency and reproducibility. UDWT efficiently decomposes spectra into noise and signal. The noise is consistent and uncorrelated. Baseline correction produces isolated peak clusters separated by flat regions. Our method reproducibly detects more peaks than the method implemented in Ciphergen software. After normalization and log transformation, the mean coefficient of variation of peak heights is 10.6%. Our method to process spectra provides improvements over existing methods. Denoising using the UDWT appears to be an important step toward obtaining results that are more accurate. It improves the reproducibility of quantifications and supplies tools for investigation of the variations in the technology more carefully. Further study will be required, because we do not have a gold standard providing an objective assessment of which peaks are present in the samples.
Coombes et al. (Thu,) studied this question.