title: A novel algorithm for validating peptide identification from a shotgun proteomics search engine.
abstract: Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has revolutionized the proteomics analysis of complexes, cells, and tissues. In a typical proteomic analysis, the tandem mass spectra from a LC-MS/MS experiment are assigned to a peptide by a search engine that compares the experimental MS/MS peptide data to theoretical peptide sequences in a protein database. The peptide spectra matches are then used to infer a list of identified proteins in the original sample. However, the search engines often fail to distinguish between correct and incorrect peptides assignments. In this study, we designed and implemented a novel algorithm called De-Noise to reduce the number of incorrect peptide matches and maximize the number of correct peptides at a fixed false discovery rate using a minimal number of scoring outputs from the SEQUEST search engine. The novel algorithm uses a three-step process: data cleaning, data refining through a SVM-based decision function, and a final data refining step based on proteolytic peptide patterns. Using proteomics data generated on different types of mass spectrometers, we optimized the De-Noise algorithm on the basis of the resolution and mass accuracy of the mass spectrometer employed in the LC-MS/MS experiment. Our results demonstrate De-Noise improves peptide identification compared to other methods used to process the peptide sequence matches assigned by SEQUEST. Because De-Noise uses a limited number of scoring attributes, it can be easily implemented with other search engines.
authors: Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.
authors: Ling
authors: L
authors: Jian
authors: Xinnan
authors: X
authors: Niu
authors: Zhonghang
authors: Z
authors: Xia
authors: Parimal
authors: P
authors: Samir
authors: Chiranthani
authors: C
authors: Sumanasekera
authors: Zheng
authors: Z
authors: Mu
authors: Jennifer L
authors: JL
authors: Jennings
authors: Kristen L
authors: KL
authors: Hoek
authors: Tara
authors: T
authors: Allos
authors: Leigh M
authors: LM
authors: Howard
authors: Kathryn M
authors: KM
authors: Edwards
authors: P Anthony
authors: PA
authors: Weil
authors: Andrew J
authors: AJ
authors: Link
mesh_terms: D000465:Algorithms; D002853:Chromatography, Liquid; D030562:Databases, Protein; D006801:Humans; D040901:Proteomics; D053719:Tandem Mass Spectrometry
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