Reinvestigating the Correctness of Decoy-Based False Discovery Rate Control in Proteomics Tandem Mass Spectrometry.
J Proteome Res
; 23(6): 1907-1914, 2024 Jun 07.
Article
em En
| MEDLINE
| ID: mdl-38687997
ABSTRACT
Traditional database search methods for the analysis of bottom-up proteomics tandem mass spectrometry (MS/MS) data are limited in their ability to detect peptides with post-translational modifications (PTMs). Recently, "open modification" database search strategies, in which the requirement that the mass of the database peptide closely matches the observed precursor mass is relaxed, have become popular as ways to find a wider variety of types of PTMs. Indeed, in one study, Kong et al. reported that the open modification search tool MSFragger can achieve higher statistical power to detect peptides than a traditional "narrow window" database search. We investigated this claim empirically and, in the process, uncovered a potential general problem with false discovery rate (FDR) control in the machine learning postprocessors Percolator and PeptideProphet. This problem might have contributed to Kong et al.'s report that their empirical results suggest that false discovery (FDR) control in the narrow window setting might generally be compromised. Indeed, reanalyzing the same data while using a more standard form of target-decoy competition-based FDR control, we found that, after accounting for chimeric spectra as well as for the inherent difference in the number of candidates in open and narrow searches, the data does not provide sufficient evidence that FDR control in proteomics MS/MS database search is inherently problematic.
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Base de dados:
MEDLINE
Assunto principal:
Processamento de Proteína Pós-Traducional
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Bases de Dados de Proteínas
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Proteômica
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Espectrometria de Massas em Tandem
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article