title: Central limit theorem as an approximation for intensity-based scoring function.
abstract: In this paper, we present an intensity-based probability function to identify peptides from tandem mass spectra and amino acid sequence databases. The function is an approximation to the central limiting theorem, and it explicitly depends on the cumulative product ion intensities, number of product ions of a peptide, and expectation value of the cumulative intensity. We compare the results of database searches using the new scoring function and scoring functions from earlier algorithms, which implement hypergeometric probability, Poisson's model, and cross-correlation scores. For a standard protein mixture (tandem mass spectra generated from the mixture of five known proteins), we generate receiver operating curves with all scoring schemes. The receiver operating curves show that the shared peaks count-based probability methods (like Poisson and hypergeometric models) are the most specific for matching high-quality tandem mass spectra. The intensity-based (central limit model) and intensity-modeled (cross-correlation) methods are more sensitive when matching low-quality tandem mass spectra, where the number of shared peaks is insufficient to correctly identify a peptide. Cross-correlation methods show a small advantage over the intensity-based probability method.
authors.affiliation: Thermo Electron Corporation, San Jose, California 95134, USA.
authors.forename: Rovshan
authors.initials: R
authors.lastname: Sadygov
authors.forename: James
authors.initials: J
authors.lastname: Wohlschlegel
authors.forename: Sung Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
mesh_terms: D000465:Algorithms; D000596:Amino Acids / Q000032:analysis; D030562:Databases, Protein; D006801:Humans; D013058:Mass Spectrometry; D015233:Models, Statistical; D010446:Peptide Fragments / Q000032:analysis*; D010449:Peptide Mapping; D011336:Probability; D011506:Proteins / Q000032:analysis*; D040901:Proteomics; D012984:Software; D016008:Statistical Distributions
chemical_list: D000596:Amino Acids; D010446:Peptide Fragments; D011506:Proteins