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A critical component in mass spectrometry (MS)-based proteomics is an accurate protein identification procedure. Database search algorithms commonly generate a list of peptide-spectrum matches (PSMs). The validity of these PSMs is critical for downstream analysis since proteins that are present in the sample are inferred from those PSMs. A variety of postprocessing algorithms have been proposed to validate and filter PSMs. Among them, the most popular ones include a semi-supervised learning (SSL) approach known as Percolator and an empirical modeling approach known as PeptideProphet. However, they are predominantly designed for commercial database search algorithms, i.e., SEQUEST and MASCOT. Therefore, it is highly desirable to extend and optimize those PSM postprocessing algorithms for open source database search algorithms such as X!Tandem. In this paper, we propose a Self-boosted Percolator for postprocessing X!Tandem search results. We find that the SSL algorithm utilized by Percolator depends heavily on the initial ranking of PSMs. Starting with a poor PSM ranking list may cause Percolator to perform suboptimally. By implementing Percolator in a cascade learning manner, we can progressively improve the performance through multiple boost runs, enabling many more PSM identifications without sacrificing false discovery rate (FDR).
Computational Biology and Bioinformatics, IEEE/ACM Transactions on (Volume:9 , Issue: 5 )
Date of Publication: Sept.-Oct. 2012