Glyco-Decipher enables glycan database-independent peptide matching and in-depth characterization of site-specific N-glycosylation

• Main Authors: Dong, M. (Author), Fang, Z. (Author), Liu, L. (Author), Mao, J. (Author), Nie, Y. (Author), Qin, H. (Author), Wang, Y. (Author), Wang, Z. (Author), Ye, M. (Author), Zhang, N. (Author)
• Format: Article
• Language: English
• Published: Nature Research 2022
• Online Access: View Fulltext in Publisher

 Glycopeptides with unusual glycans or poor peptide backbone fragmentation in tandem mass spectrometry are unaccounted for in typical site-specific glycoproteomics analysis and thus remain unidentified. Here, we develop a glycoproteomics tool, Glyco-Decipher, to address these issues. Glyco-Decipher conducts glycan database-independent peptide matching and exploits the fragmentation pattern of shared peptide backbones in glycopeptides to improve the spectrum interpretation. We benchmark Glyco-Decipher on several large-scale datasets, demonstrating that it identifies more peptide-spectrum matches than Byonic, MSFragger-Glyco, StrucGP and pGlyco 3.0, with a 33.5%-178.5% increase in the number of identified glycopeptide spectra. The database-independent and unbiased profiling of attached glycans enables the discovery of 164 modified glycans in mouse tissues, including glycans with chemical or biological modifications. By enabling in-depth characterization of site-specific protein glycosylation, Glyco-Decipher is a promising tool for advancing glycoproteomics analysis in biological research. © 2022, The Author(s).