Bridging the False Discovery Gap

J Proteome Res. 2023 Jul 7;22(7):2172-2178. doi: 10.1021/acs.jproteome.3c00176. Epub 2023 Jun 1.

Abstract

Controlling the false discovery rate (FDR) among discoveries from a tandem mass spectrometry proteomics experiment using target decoy competition (TDC) controls only the proportion of false discoveries in an average sense. Thus, for any particular analysis, even with a valid FDR control procedure, the proportion of false discoveries (the FDP) may be higher than the specified FDR threshold. We demonstrate this phenomenon using real data and describe two recently developed methods that help bridge the gap between controlling the expected or average rate of false discoveries and the empirical rate (FDP). The FDP Stepdown method controls the FDP at any desired confidence level, and the TDC Uniform Band provides a confidence, or upper prediction bound, on the FDP in TDC's list of discoveries.

Keywords: false discovery proportion; false discovery rate; peptide detection; target-decoy competition.

MeSH terms

  • Algorithms*
  • Databases, Protein
  • Proteomics* / methods
  • Tandem Mass Spectrometry