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Improving Phosphopeptide/Protein Identification Using a New Data Mining Framework for MS/MS Spectra Preprocessing

Fabio R. Cerqueira1,*, Sandra Morandell2, Stefan Ascher2, Karl Mechtler3, Lukas A. Huber2, Bernhard Pfeifer1, Armin Graber4, Bernhard Tilg1, Christian Baumgartner1,*
1Research Group for Clinical Bioinformatics, Institute of Biomedical Engineering, University for Health Sciences, Medical Informatics and Technology, Eduard Wallnoefer Zentrum 1, 6060, Hall in Tirol, Austria
2Biocenter, Division of Cell Biology, Medical University of Innsbruck, Fritz-Pregl Str. 3, 6020, Innsbruck, Austria
3Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7 and Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr Gasse 3, A1030 Vienna, Austria
4Institute for Bioinformatics, University for Health Sciences, Medical Informatics and Technology, Eduard Wallnoefer Zentrum 1, 6060, Hall in Tirol, Austria
*Corresponding author: Fabio R. Cerqueira, Research Group for Clinical Bioinformatics,
Institute of Biomedical Engineering, University for Health Sciences,
Medical Informatics and Technology,
Eduard Wallnoefer Zentrum 1, 6060, Hall in Tirol, Austria,
Phone: +43 50 8648 3827,
Fax: +43 50 8648 673827,
E-mail: fabio.cerqueira@umit.at
Christian Baumgartner, Research Group for Clinical Bioinformatics,
Institute of Biomedical Engineering, University for Health Sciences,
Medical Informatics and Technology, Eduard Wallnoefer Zentrum 1, 6060,
Hall in Tirol, Austria,
E-mail: christian.baumgartner@umit.at
Received January 27, 2009; Accepted March 21, 2009; Published March 21, 2009
Citation:Cerqueira FR, Morandell S, Ascher S, Mechtler K, Huber LA, et al. (2009) Improving Phosphopeptide/protein Identification using a New Data Mining Framework for MS/MS Spectra Preprocessing. J Proteomics Bioinform 2: 150-164. doi:10.4172/jpb.1000072
Copyright: © 2009 Cerqueira FR, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract

Phosphopeptide/protein Identification using tandem mass spectrometry (MS/MS) is a challenging issue in proteomics research. In particular, phosphopeptides typically exhibit low intensity peaks of b and y ions in spectra when serine or threonine is phosphorylated. Consequently, the existing algorithms for peptide and protein Identification generate a high false discovery rate when coping with phosphopeptide spectra. In order to increase the number of correct phosphopeptide Identification using database search, a new data mining approach for spectra preprocessing is proposed. A support vector machine classifier is used to calculate the probability of each peak representing a b or y ion. Next, low-probability peaks are removed from spectra, while remaining peaks have their intensities enhanced. As a result, a huge increase in signal-to-noise ratio is provided and the chances of detecting important peaks are significantly advanced. Experiments using MASCOT and SEQUEST along with Peptide/ProteinProphet and a decoy database approach showed a significant improvement in the sensitivity of phosphopeptide Identification without compromising specificity, demonstrating that our new strategy for MS/MS spectra preprocessing is a powerful proteomics tool for enhancing phosphopeptide Identification.

 
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