Unbiased false discovery rate estimation for shotgun proteomics based on the target-decoy approach

LI Levitsky, MV Ivanov, AA Lobas… - Journal of proteome …, 2017 - ACS Publications
Journal of proteome research, 2017ACS Publications
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 …
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.
ACS Publications
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