GlyGen growth and evolution into a central resource for glycans and glycoconjugates

摘要 GlyGen是一个成熟的(五年前)的知识库，它积累了糖生物学领域的数据，并 将其与其他数据类型连接。GlyGen是独一无二的；目前或以前没有其他信息资源 这样一项综合性的任务。在某种程度上，糖生物学领域可获得的知识增长滞后， 与其他组学或生物医学研究领域相比，反映了多糖结构的固有复杂性， 与基因和蛋白质不同，它以分支和异构体的形式存在，其生物合成不能归因于 特征明确、模板驱动的流程，如转录或翻译。相反，多聚糖的生物合成 是由糖基转移酶、底物转运体和 分泌途径调节机制共同产生动态的细胞和组织特异性模式 蛋白质和脂肪糖基化。此外，糖蛋白上的每个糖基化位点都可能被常规修饰。 通过一系列的糖链结构之一，糖蛋白的一种特性称为微异质性。重要的是 微观异质性不是随机的，而是反映特定细胞和组织的内在生物合成能力。 可能会因疾病而改变。这些结构和生物合成的复杂性是导致 糖链和糖基化的组织和疾病特异性功能，因此，需要捕获和 以可被查询和链接到其他类型的数据的方式在知识库中表示。绿色基因 旨在扩展其基础数据模型，以适应新的和更复杂的数据类型，增强和 集成新的数据类型，并实施健壮的建模、统一的过程和工具以改进 发现和探索糖和糖共轭数据。增强整体资源功能 将通过前端改进实现，以适应用户偏好并确保卓越的数据 沟通和可视化。改善GlyGen及其合作伙伴数据库的互联互通 加强资源间的数据共享将继续是GlyGen项目的核心原则。所有由此产生的 统一的数据将通过高度许可的许可证提供，以便轻松整合到其他资源中， 例如NCBI、EBI、SIB和其他国际努力，以及便于独立机构重新调整用途 研究人员、教育工作者、生物信息学家和商业实体。到下一个项目期结束时，GlyGen 预计将成为糖科学数据的首选、整合良好的资源，类似于现有的蛋白质和 基因组资源，并为同样广泛的生物医学研究人员社区服务。

ABSTRACT GlyGen is a maturing (five years old) knowledgebase that accumulates data in the glycobiology domain and connects it with other data types. GlyGen is unique; no other present or prior informatic resource has undertaken such an integrative mission. In part, the lagging growth of accessible knowledge in the glycobiology domain, compared to other -omics or biomedical research fields, reflects the inherent complexity of glycan structures, which, unlike genes and proteins, exist in branched and isomeric forms whose biosynthesis is not attributable to well-characterized, template-driven processes such as transcription or translation. Rather, glycan biosynthesis is mediated by the regulated expression of ensembles of glycosyltransferases, substrate transporters, and secretory pathway regulatory mechanisms that together generate dynamic cell- and tissue-specific patterns of protein and lipid glycosylation. In addition, each glycosylation site on a glycoprotein may routinely be modified by one of an ensemble of glycan structures, a glycoprotein feature called microheterogeneity. Importantly, microheterogeneity is not random, but reflects the intrinsic biosynthetic capacity of specific cells and tissues and may be modified by disease. These structural and biosynthetic complexities are essential contributors to the tissue- and disease-specific functions of glycans and glycosylation, and, therefore, need to be captured and represented in knowledgebases in a way that they can be queried and linked to other types of data. GlyGen aims to expand its underlying data model to accommodate new and more complex datatypes, augmenting and integrating new data types, and implementing robust modeling, unified procedures, and tools to improve discovery and exploration of glycan and glycoconjugate data. Enhancement of the overall resource functionality will be achieved through front-end improvements to accommodate user preferences and ensure exceptional data communication and visualization. Improving the interconnectivity of GlyGen and its partner databases as well as enhancing data-sharing across resources will continue to be core principles of the GlyGen project. All resulting harmonized data will be available through highly permissive licenses for easy integration into other resources, such as NCBI, EBI, SIB and other international efforts, as well as for easy repurposing by independent researchers, educators, bioinformaticians, and commercial entities. By the end of the next project period GlyGen expects to become the go-to, well-integrated resource for glycoscience data, similar to existing protein and genomic resources and serving the same broad community of biomedical researchers.