Aberrant glycosylation has been commonly observed in various physiological and pathological disorders (including cancers), and quite a few glycoproteins have been approved by the US Food and Drug Administration (FDA) as markers for early diagnosis. Each glycoprotein may have multiple glycoforms, and cancer-related ones can be only some specific glycoforms which have much higher sensitivity and specificity; for example, AFP glycoform AFP-L3 with N-glycan of 01Y(61F)41Y41M(31M41Y41L41S61M41Y41L41S is of bigger diagnostic value for hepatocellular carcinoma than total AFP (i.e., combination of all glycoforms). Mass spectrometry-based glycomics is currently the state-of-the-art instrumental analytical pipeline for high-throughput characterization of various glycoforms, where not only monosaccharide composition but also comprehensive structural information (sequence and linkage) of N-glycans are now reported thanks to our recently developed N-glycan database search engine GlySeeker. With this new capability, here, we report our large-scale characterization of human liver N-glycome with primary structures; 214 unique N-glycans with unique primary structures were identified and visualized with spectrum-level false discovery rate ≤ 1% and number of best hits of 1. The LO2 N-glycans reported here serve as a basic reference for future liver N-glycome study, and further quantitative analysis will enable characterization of differentially expressed N-glycans and discovery of more effective markers for liver and other diseases. Data are available via ProteomeXchange with identifier PXD008158.

中文翻译：

---

从LO2细胞富集的人类肝脏N糖基的大规模鉴定和可视化

异常糖基化通常在各种生理和病理性疾病（包括癌症）中观察到，并且相当多的糖蛋白已被美国食品和药物管理局（FDA）批准作为早期诊断的标志物。每个糖蛋白可能具有多种糖型，而与癌症相关的糖蛋白可能只是一些具有更高敏感性和特异性的特定糖型。例如，NFP为01Y（61F）41Y41M（31M41Y41L41S61M41Y41L41S）的AFP糖型AFP-L3对肝细胞癌的诊断价值要高于总AFP（即所有糖型的组合）。最先进的仪器分析管线，可高通量表征各种糖型，由于我们最近开发的N-聚糖数据库搜索引擎GlySeeker，现在不仅报道了N-聚糖的单糖成分，而且还报道了其全面的结构信息（序列和连接）。借助这项新功能，我们在这里报告了我们具有一级结构的人类肝脏N-糖基的大规模表征。鉴定并可视化了214种具有独特一级结构的独特N-聚糖，其频谱级错误发现率≤1％，最佳匹配数为1。此处报道的LO2 N-聚糖可作为未来肝N-糖组研究的基本参考，以及进一步的定量分析将有助于表征差异表达的N-聚糖，并发现更有效的肝脏和其他疾病标记物。数据可通过ProteomeXchange获得，其标识符为PXD008158。