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Beyond target-decoy competition: stable validation of peptide and protein identifications in mass spectrometry-based discovery proteomics

Yohann Couté, Christophe Bruley, View ORCID ProfileThomas Burger
doi: https://doi.org/10.1101/765057
Yohann Couté
†Univ. Grenoble Alpes, CNRS, CEA, INSERM, IRIG, BGE, F-38000 Grenoble, France
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Christophe Bruley
†Univ. Grenoble Alpes, CNRS, CEA, INSERM, IRIG, BGE, F-38000 Grenoble, France
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Thomas Burger
†Univ. Grenoble Alpes, CNRS, CEA, INSERM, IRIG, BGE, F-38000 Grenoble, France
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  • ORCID record for Thomas Burger
  • For correspondence: thomas.burger@cea.fr
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Abstract

In bottom-up discovery proteomics, target-decoy competition (TDC) is the most popular method for false discovery rate (FDR) control. Despite unquestionable statistical foundations, this method has drawbacks, including its hitherto unknown intrinsic lack of stability vis-à-vis practical conditions of application. Although some consequences of this instability have already been empirically described, they may have been misinter-preted. This article provides evidence that TDC has become less reliable as the accuracy of modern mass spectrometers improved. We therefore propose to replace TDC by a totally different method to control the FDR at spectrum, peptide and protein levels, while benefiting from the theoretical guarantees of the Benjamini-Hochberg framework. As this method is simpler to use, faster to compute and more stable than TDC, we argue that it is better adapted to the standardization and throughput constraints of current proteomic platforms.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 08, 2020.
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Beyond target-decoy competition: stable validation of peptide and protein identifications in mass spectrometry-based discovery proteomics
Yohann Couté, Christophe Bruley, Thomas Burger
bioRxiv 765057; doi: https://doi.org/10.1101/765057
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Beyond target-decoy competition: stable validation of peptide and protein identifications in mass spectrometry-based discovery proteomics
Yohann Couté, Christophe Bruley, Thomas Burger
bioRxiv 765057; doi: https://doi.org/10.1101/765057

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