title: Computational prediction of proteotypic peptides for quantitative proteomics.
abstract: Mass spectrometry-based quantitative proteomics has become an important component of biological and clinical research. Although such analyses typically assume that a protein's peptide fragments are observed with equal likelihood, only a few so-called 'proteotypic' peptides are repeatedly and consistently identified for any given protein present in a mixture. Using >600,000 peptide identifications generated by four proteomic platforms, we empirically identified >16,000 proteotypic peptides for 4,030 distinct yeast proteins. Characteristic physicochemical properties of these peptides were used to develop a computational tool that can predict proteotypic peptides for any protein from any organism, for a given platform, with >85% cumulative accuracy. Possible applications of proteotypic peptides include validation of protein identifications, absolute quantification of proteins, annotation of coding sequences in genomes, and characterization of the physical principles governing key elements of mass spectrometric workflows (e.g., digestion, chromatography, ionization and fragmentation).
authors.affiliation: Institute for Systems Biology, 1441 N. 34th Street, Seattle, Washington 98103, USA.
authors.forename: Parag
authors.initials: P
authors.lastname: Mallick
authors.forename: Markus
authors.initials: M
authors.lastname: Schirle
authors.forename: Sharon S
authors.initials: SS
authors.lastname: Chen
authors.forename: Mark R
authors.initials: MR
authors.lastname: Flory
authors.forename: Hookeun
authors.initials: H
authors.lastname: Lee
authors.forename: Daniel
authors.initials: D
authors.lastname: Martin
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ranish
authors.forename: Brian
authors.initials: B
authors.lastname: Raught
authors.forename: Robert
authors.initials: R
authors.lastname: Schmitt
authors.forename: Thilo
authors.initials: T
authors.lastname: Werner
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kuster
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
mesh_terms: D000465:Algorithms; D020869:Gene Expression Profiling / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D010449:Peptide Mapping / Q000379:methods*; D010455:Peptides / Q000032:analysis / Q000737:chemistry*; D020543:Proteome / Q000032:analysis / Q000737:chemistry*; D020539:Sequence Analysis, Protein / Q000379:methods*
chemical_list: D010455:Peptides; D020543:Proteome