Theoretical assessment of indistinguishable peptides in mass spectrometry-based proteomics

Mass-spectrometry-based proteomics has advanced with the integration of experimental and predicted spectral libraries, which have significantly improved peptide identification in complex search spaces. However, challenges persist in distinguishing some peptides with close retention times and nearly...

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Bibliographic Details
Authors: Elhamraoui, Zahra, Borràs, Eva, Wilhelm, Mathias, Sabidó Aguadé, Eduard, 1981-
Format: article
Status:Published version
Publication Date:2024
Country:España
Institution:Universitat Pompeu Fabra
Repository:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/68925
Online Access:http://hdl.handle.net/10230/68925
http://dx.doi.org/10.1021/acs.analchem.4c02803
Access Level:Open access
Keyword:Fragmentation
Monomers
Peptide identification
Peptides and proteins
Precursors
Description
Summary:Mass-spectrometry-based proteomics has advanced with the integration of experimental and predicted spectral libraries, which have significantly improved peptide identification in complex search spaces. However, challenges persist in distinguishing some peptides with close retention times and nearly identical fragmentation patterns. In this study, we conducted a theoretical assessment to quantify the prevalence of indistinguishable peptides within the human canonical proteome and immunopeptidome using state-of-the-art retention time and spectrum prediction models. By quantifying the proportion of peptides posing challenges to unequivocal identification, we set the theoretical nonaccessible portion within a given proteome, and underscore the effectiveness of contemporary analytical methodologies in resolving the complexity of the human proteome and immunopeptidome via mass spectrometry.