title: Rapid and accurate peptide identification from tandem mass spectra.
abstract: Mass spectrometry, the core technology in the field of proteomics, promises to enable scientists to identify and quantify the entire complement of proteins in a complex biological sample. Currently, the primary bottleneck in this type of experiment is computational. Existing algorithms for interpreting mass spectra are slow and fail to identify a large proportion of the given spectra. We describe a database search program called Crux that reimplements and extends the widely used database search program Sequest. For speed, Crux uses a peptide indexing scheme to rapidly retrieve candidate peptides for a given spectrum. For each peptide in the target database, Crux generates shuffled decoy peptides on the fly, providing a good null model and, hence, accurate false discovery rate estimates. Crux also implements two recently described postprocessing methods: a p value calculation based upon fitting a Weibull distribution to the observed scores, and a semisupervised method that learns to discriminate between target and decoy matches. Both methods significantly improve the overall rate of peptide identification. Crux is implemented in C and is distributed with source code freely to noncommercial users.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Park
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Klammer
authors.forename: Lukas
authors.initials: L
authors.lastname: Käll
authors.forename: Michael J
authors.initials: MJ
authors.lastname: MacCoss
authors.forename: William S
authors.initials: WS
authors.lastname: Noble
mesh_terms: D000465:Algorithms; D019295:Computational Biology; D016208:Databases, Factual; D006801:Humans; D010446:Peptide Fragments / Q000032:analysis; D010455:Peptides / Q000032:analysis*; D040901:Proteomics; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis; D012984:Software; D053719:Tandem Mass Spectrometry
chemical_list: D010446:Peptide Fragments; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins