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Bridging the False Discovery Gap.

Arya Ebadi1, Jack Freestone1, William S Noble2,3

  • 1School of Mathematics and Statistics F07, University of Sydney, Sydney, New South Wales 2006, Australia.

Journal of Proteome Research
|June 1, 2023
PubMed
Summary
This summary is machine-generated.

False discovery rate (FDR) control in proteomics experiments using target decoy competition (TDC) may not guarantee low false discovery proportions (FDP) in specific analyses. New methods like FDP Stepdown and TDC Uniform Band offer better control over empirical FDP.

Keywords:
false discovery proportionfalse discovery ratepeptide detectiontarget-decoy competition

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Area of Science:

  • Proteomics
  • Bioinformatics
  • Statistical analysis

Background:

  • Tandem mass spectrometry proteomics experiments generate large datasets.
  • Target decoy competition (TDC) is a common method for controlling the false discovery rate (FDR).
  • Standard FDR control methods manage the average proportion of false discoveries, not the empirical proportion in a specific dataset.

Purpose of the Study:

  • To highlight the discrepancy between average FDR control and empirical false discovery proportion (FDP) in proteomics.
  • To introduce and explain two novel statistical methods for improved FDP control.

Main Methods:

  • Demonstration of the FDR vs. FDP phenomenon using real proteomics data.
  • Description of the FDP Stepdown method for controlling empirical FDP at a specified confidence level.
  • Explanation of the TDC Uniform Band method for providing upper bounds on FDP.

Main Results:

  • Real data analysis confirmed that average FDR control does not guarantee low empirical FDP.
  • The FDP Stepdown method was shown to effectively control the empirical FDP.
  • The TDC Uniform Band provides a statistically sound confidence bound for the FDP.

Conclusions:

  • Standard FDR control in proteomics can lead to higher-than-expected false discovery proportions in practice.
  • The FDP Stepdown and TDC Uniform Band methods offer more reliable control over the actual number of false discoveries.
  • These new methods enhance the trustworthiness of findings in mass spectrometry proteomics.