title: Unbiased False Discovery Rate Estimation for Shotgun Proteomics Based on the Target-Decoy Approach.
abstract: Target-decoy approach (TDA) is the dominant strategy for false discovery rate (FDR) estimation in mass-spectrometry-based proteomics. One of its main applications is direct FDR estimation based on counting of decoy matches above a certain score threshold. The corresponding equations are widely employed for filtering of peptide or protein identifications. In this work we consider a probability model describing the filtering process and find that, when decoy counting is used for q value estimation and subsequent filtering, a correction has to be introduced into these common equations for TDA-based FDR estimation. We also discuss the scale of variance of false discovery proportion (FDP) and propose using confidence intervals for more conservative FDP estimation in shotgun proteomics. The necessity of both the correction and the use of confidence intervals is especially pronounced when filtering small sets (such as in proteogenomics experiments) and when using very low FDR thresholds.
authors.affiliation: Moscow Institute of Physics and Technology , Dolgoprudny, Moscow Region 141701, Russia.|V.L. Talrose Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences , Moscow 119991, Russia.
authors.forename: Lev I
authors.initials: LI
authors.lastname: Levitsky
authors.affiliation: Moscow Institute of Physics and Technology , Dolgoprudny, Moscow Region 141701, Russia.|V.L. Talrose Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences , Moscow 119991, Russia.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Ivanov
authors.affiliation: Moscow Institute of Physics and Technology , Dolgoprudny, Moscow Region 141701, Russia.|V.L. Talrose Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences , Moscow 119991, Russia.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Lobas
authors.affiliation: Moscow Institute of Physics and Technology , Dolgoprudny, Moscow Region 141701, Russia.|V.L. Talrose Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences , Moscow 119991, Russia.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Gorshkov
mesh_terms: D000465:Algorithms; D030562:Databases, Protein; D015233:Models, Statistical; D011506:Proteins / Q000032:analysis*; D040901:Proteomics / Q000706:statistics & numerical data*; D053719:Tandem Mass Spectrometry
chemical_list: D011506:Proteins
keywords: false discovery rate; proteomics; target-decoy approach