Discovery of Protein Modifications Using Differential Tandem Mass Spectrometry Proteomics

Cifani, Paolo, Li, Zhi, Luo, Danmeng, Grivainis, Mark, Intlekofer, Andrew M, Fenyö, David, Kentsis, Alex (April 2021) Discovery of Protein Modifications Using Differential Tandem Mass Spectrometry Proteomics. Journal of Proteome Research, 20 (4). pp. 1835-1848. ISSN 1535-3893

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).

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics Investigative techniques and equipment bioinformatics > computational biology > algorithms organism description > animal organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell signaling bioinformatics > computational biology organism description > animal > mammal Investigative techniques and equipment > spectroscopy > mass spectrometry organism description > animal > mammal > rodent > mouse bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > post-translational modification organism description > animal > mammal > rodent Investigative techniques and equipment > spectroscopy
CSHL Authors:	Cifani, Paolo
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2 April 2021
Date Deposited:	31 Jan 2023 16:56
Last Modified:	23 Jan 2024 19:22
PMCID:	PMC8341206
Related URLs:	PubMed
URI:	https://repository.cshl.edu/id/eprint/40811

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