sensitive and specific peak detection for seldi-tof mass spectrometry using a waveletneural-network based approach敏感和特异峰检测使用一个基于waveletneural-network seldi-tof质谱方法.pdfVIP

Sensitive and Specific Peak Detection for SELDI-TOF Mass Spectrometry Using a Wavelet/Neural-Network Based Approach Vincent A. Emanuele II*, Gitika Panicker, Brian M. Gurbaxani, Jin-Mann S. Lin, Elizabeth R. Unger Chronic and Viral Diseases Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America Abstract SELDI-TOF mass spectrometer’s compact size and automated, high throughput design have been attractive to clinical researchers, and the platform has seen steady-use in biomarker studies. Despite new algorithms and preprocessing pipelines that have been developed to address reproducibility issues, visual inspection of the results of SELDI spectra preprocessing by the best algorithms still shows miscalled peaks and systematic sources of error. This suggests that there continues to be problems with SELDI preprocessing. In this work, we study the preprocessing of SELDI in detail and introduce improvements. While many algorithms, including the vendor supplied software, can identify peak clusters of specific mass (or m/z) in groups of spectra with high specificity and low false discover rate (FDR), the algorithms tend to underperform estimating the exact prevalence and intensity of peaks in those clusters. Thus group differences that at first appear very strong are shown, after careful and laborious hand inspection of the spectra, to be less than significant. Here we introduce a wavelet/neural network based algorithm which mimics what a team of expert, human users would call for peaks in each of several hundred spectra in a typical SELDI clinical study. The wavelet denoising part of the algorithm optimally smoothes the signal in each spectr