蛋白质组学
计算生物学
串联质谱法
串联质量标签
质谱法
定量蛋白质组学
蛋白质法
鸟枪蛋白质组学
药物发现
肽
生物标志物发现
化学
半胱氨酸
翻译后修饰
色谱法
生物
肽序列
生物化学
基因
酶
作者
Paolo Cifani,Zhi Li,Danmeng Luo,Mark Grivainis,Andrew M. Intlekofer,David Fenyö,Alex Kentsis
标识
DOI:10.1021/acs.jproteome.0c00638
摘要
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).
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