A Strategy for Precise and Large Scale Identification of Core Fucosylated Glycoproteins
A Strategy for Precise and Large Scale Identification of Core Fucosylated Glycoproteins
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DOI：
10.1074/mcp.m800504-mcp200
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发表时间：
2009-05-01
影响因子：
7
通讯作者：
Qian, Xiao-Hong
中科院分区：
文献类型：
--
作者：
Jia, Wei;Lu, Zhuang;Qian, Xiao-Hong
一些糖蛋白的核心岩藻糖基化 (CF) 模式比评估其各自的总蛋白水平更敏感和特异，可诊断许多疾病，例如癌症。 CF 糖蛋白的整体分析和定量表征可能会揭示临床应用的有效生物标志物。然而，目前的技术无法大规模精确地揭示CF糖蛋白。在这里，我们开发了一种强大的策略，集成了分子量截止、中性损失依赖性 MS3、独立于数据库的候选谱过滤和优化，以有效识别 CF 糖蛋白。光谱处理的基本原理创新性地基于 CF 糖肽光谱中质量分布的计算。通过对健康受试者和肝细胞癌受试者的血浆进行实施，证明了该策略的有效性。鉴定了 100 多个 CF 糖蛋白和 CF 位点，发现了 10,000 多个 CF 糖肽质谱。鉴定结果的规模表明在寻找具有独特且有吸引力的前景的生物标志物方面取得了巨大进展，候选谱图将成为改进糖肽数据库搜索方法的有用资源。分子与细胞蛋白质组学 8：913-923，2009。
Core fucosylation (CF) patterns of some glycoproteins are more sensitive and specific than evaluation of their total respective protein levels for diagnosis of many diseases, such as cancers. Global profiling and quantitative characterization of CF glycoproteins may reveal potent biomarkers for clinical applications. However, current techniques are unable to reveal CF glycoproteins precisely on a large scale. Here we developed a robust strategy that integrates molecular weight cutoff, neutral loss-dependent MS3, database-independent candidate spectrum filtering, and optimization to effectively identify CF glycoproteins. The rationale for spectrum treatment was innovatively based on computation of the mass distribution in spectra of CF glycopeptides. The efficacy of this strategy was demonstrated by implementation for plasma from healthy subjects and subjects with hepatocellular carcinoma. Over 100 CF glycoproteins and CF sites were identified, and over 10,000 mass spectra of CF glycopeptide were found. The scale of identification results indicates great progress for finding biomarkers with a particular and attractive prospect, and the candidate spectra will be a useful resource for the improvement of database searching methods for glycopeptides. Molecular & Cellular Proteomics 8: 913-923, 2009.