CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023, Dalian, China.
University of Chinese Academy of Sciences, 100049, Beijing, China.
Nat Commun. 2022 Apr 7;13(1):1900. doi: 10.1038/s41467-022-29530-y.
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.
糖肽在串联质谱中具有不寻常的聚糖或较差的肽骨架碎裂，在典型的位点特异性糖蛋白质组学分析中无法解释，因此仍然未被识别。在这里，我们开发了一种糖蛋白质组学工具 Glyco-Decipher，以解决这些问题。Glyco-Decipher 进行聚糖数据库独立的肽匹配，并利用糖肽中共享肽骨架的碎裂模式来改进谱解释。我们在几个大型数据集上对 Glyco-Decipher 进行了基准测试，结果表明它比 Byonic、MSFragger-Glyco、StrucGP 和 pGlyco 3.0 识别出更多的肽谱匹配，鉴定的糖肽谱数量增加了 33.5%-178.5%。对附着聚糖的无数据库和无偏分析使我们能够在小鼠组织中发现 164 种修饰聚糖，包括具有化学或生物学修饰的聚糖。通过实现对位点特异性蛋白质糖基化的深入表征，Glyco-Decipher 是推进生物研究中糖蛋白质组学分析的有前途的工具。
