Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-2 (of 2 Records) |
Query Trace: Emanuele VA[original query] |
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Sensitive and specific peak detection for SELDI-TOF mass spectrometry using a wavelet/neural-network based approach
Emanuele VA , Panicker G , Gurbaxani BM , Lin JM , Unger ER . PLoS One 2012 7 (11) e48103 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 spectrum according to an improved suite of signal processing algorithms previously reported (the LibSELDI toolbox under development). The neural network part of the algorithm combines those results with the raw signal and a training dataset of expertly called peaks, to call peaks in a test set of spectra with approximately 95% accuracy. The new method was applied to data collected from a study of cervical mucus for the early detection of cervical cancer in HPV infected women. The method shows promise in addressing the ongoing SELDI reproducibility issues. |
Quadratic variance models for adaptively preprocessing SELDI-TOF mass spectrometry data
Emanuele VA 2nd , Gurbaxani BM . BMC Bioinformatics 2010 11 512 BACKGROUND: Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI) is a proteomics tool for biomarker discovery and other high throughput applications. Previous studies have identified various areas for improvement in preprocessing algorithms used for protein peak detection. Bottom-up approaches to preprocessing that emphasize modeling SELDI data acquisition are promising avenues of research to find the needed improvements in reproducibility. RESULTS: We studied the properties of the SELDI detector intensity response to matrix only runs. The intensity fluctuations and noise observed can be characterized by a natural exponential family with quadratic variance function (NEF-QVF) class of distributions. These include as special cases many common distributions arising in practice (e.g.- normal, Poisson). Taking this model into account, we present a modified Antoniadis-Sapatinas wavelet denoising algorithm as the core of our preprocessing program, implemented in MATLAB. The proposed preprocessing approach shows superior peak detection sensitivity compared to MassSpecWavelet for false discovery rate (FDR) values less than 25%. CONCLUSIONS: The NEF-QVF detector model requires that certain parameters be measured from matrix only spectra, leaving implications for new experiment design at the trade-off of slightly increased cost. These additional measurements allow our preprocessing program to adapt to changing noise characteristics arising from intralaboratory and across-laboratory factors. With further development, this approach may lead to improved peak prediction reproducibility and nearly automated, high throughput preprocessing of SELDI data. |
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