Discovery of protein modifications using high resolution differential mass spectrometry proteomics
Discovery of protein modifications using high resolution differential mass spectrometry proteomics
Summary Recent studies have revealed diverse amino acid, post-translational and non-canonical 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 sub-stoichiometric 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 parameterization 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).
Kentsis Alex、Cifani Paolo、Li Zhi、Luo Danmeng、Grivainis Mark、Feny? David、Intlekofer Andrew M.
Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center||Department of Pediatrics, Memorial Sloan Kettering Cancer Center, and Departments of Pediatrics, Pharmacology, and Physiology & Biophysics, Weill Medical College of Cornell UniversityMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer CenterInstitute for Systems Genetics, NYU Grossman School of Medicine||Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of MedicineMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer CenterInstitute for Systems Genetics, NYU Grossman School of MedicineInstitute for Systems Genetics, NYU Grossman School of Medicine||Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of MedicineHuman Oncology & Pathogenesis Program and Department of Medicine, Memorial Sloan Kettering Cancer Center
生物科学研究方法、生物科学研究技术生物化学分子生物学
Post-translational chemical modificationProteomicsMass-spectrometryFunctional regulationSignalingSoftwareItaconateMacrophagesMetabolismSAMPEI
Kentsis Alex,Cifani Paolo,Li Zhi,Luo Danmeng,Grivainis Mark,Feny? David,Intlekofer Andrew M..Discovery of protein modifications using high resolution differential mass spectrometry proteomics[EB/OL].(2025-03-28)[2025-06-24].https://www.biorxiv.org/content/10.1101/2020.06.19.162321.点此复制
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