Discovery of protein modifications using differential tandem mass spectrometry proteomics Journal Article


Authors: Cifani, P.; Li, Z.; Luo, D.; Grivainis, M.; Intlekofer, A. M.; Fenyö, D.; Kentsis, A.
Article Title: Discovery of protein modifications using differential tandem mass spectrometry proteomics
Abstract: Recent studies have revealed diverse amino acid, post-translational, and noncanonical modifications of proteins in diverse organisms and tissues. However, their unbiased detection and analysis remain hindered by technical limitations. Here, we present a spectral alignment method for the identification of protein modifications using high-resolution mass spectrometry proteomics. Termed SAMPEI for spectral alignment-based modified peptide identification, this open-source algorithm is designed for the discovery of functional protein and peptide signaling modifications, without prior knowledge of their identities. Using synthetic standards and controlled chemical labeling experiments, we demonstrate its high specificity and sensitivity for the discovery of substoichiometric protein modifications in complex cellular extracts. SAMPEI mapping of mouse macrophage differentiation revealed diverse post-translational protein modifications, including distinct forms of cysteine itaconatylation. SAMPEI's robust parametrization and versatility are expected to facilitate the discovery of biological modifications of diverse macromolecules. SAMPEI is implemented as a Python package and is available open-source from BioConda and GitHub (https://github.com/FenyoLab/SAMPEI).
Keywords: mass spectrometry; metabolism; signaling; macrophages; software; functional regulation; post-translational chemical modification; itaconate; sampei; spectral alignment
Journal Title: Journal of Proteome Research
Volume: 20
Issue: 4
ISSN: 1535-3893
Publisher: American Chemical Society  
Date Published: 2021-04-02
Start Page: 1835
End Page: 1848
Language: English
DOI: 10.1021/acs.jproteome.0c00638
PUBMED: 33749263
PROVIDER: scopus
PMCID: PMC8341206
DOI/URL:
Notes: Article -- Export Date: 3 May 2021 -- Source: Scopus
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  1. Alex   Kentsis
    103 Kentsis
  2. Paolo   Cifani
    32 Cifani
  3. Danmeng Luo
    1 Luo