Functional Annotation of Glycan Motifs using Common-Fund Data Resources

使用共同基金数据资源对聚糖基序进行功能注释

• 批准号: 10576685
• 负责人: NATHAN J EDWARDS
• 金额: $ 31.2万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2024-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10576685
• 关键词: Automobile Driving; Binding; Binding Proteins; Biological; Catalogs; Cell Communication; Cells; Collection; Complement; Data; Enzymes; Funding; Genes; Genotype-Tissue Expression Project; Glycoproteins; Glycoside Hydrolases; Golgi Apparatus; Heterogeneity; Human; Immune response; Individual; Infrastructure; International; Manuals; Monosaccharides; Mus; Names; Phenotype; Play; Polysaccharides; Proteins; Publications; Resources; Role; Signal Transduction; Structure; Tertiary Protein Structure; Testing; Tissues; base; cell type; data resource; glycosylation; glycosyltransferase; heuristics; insight; knowledgebase

Abstract Glycans play an important role in cell-cell interaction, cell-signaling, and immune response, with specific glycan structural motifs responsible for driving glycans’ cell- and protein- binding activity and thus their functional role. Despite glycans’ significant structural heterogeneity, these glycan motifs, or determinants, have been recognized as relevant in specific biological contexts and named by glycobiologists. In a similar way as protein domains, these recurring structural motifs confer specific binding and functional activity to glycan structures that contain them. Many collections and catalogs of these glycan motifs have been developed but they are primarily lists – little to no functional understanding is captured by these resources to provide biological context for understanding a motifs’ role in the cell. The GlycoMotif data- resource, developed in the Edwards lab in support of the GlyGen Glycan Knowledgebase, a Common- Fund sponsored data-resource, is one such catalog of glycan motifs, with the capability to annotate each motif with names, keywords, and publications. Despite the relative paucity of our understanding of glycan structure motifs’ functions, however, we do understand the glycosylation enzyme machinery responsible for assembling and attaching glycans to glycoproteins, and can enumerate, though the data-resources provided by GlyGen, the glycoenzymes necessary for attaching and assembling mature glycan structures on mouse and human proteins. We seek to explore the utility of functional annotation of GlycoMotif glycan motifs by the integration of gene-based phenotype, tissue-localization, and cell-type annotations of associated glycoenzymes from the International Mouse Phenotyping Consortium and GTEx Common- Fund data-resources with GlycoMotif, and thereby providing a platform for comprehensive functional annotation of glycan motifs, and ultimately, glycan structures in GlyGen.

抽象的 聚糖在细胞细胞相互作用，细胞信号和免疫响应中起着重要作用， 聚糖结构基序负责驱动聚糖的细胞和蛋白质结合活性，从而 功能作用。尽管聚糖具有显着的结构异质性，但这些聚糖基序或确定词， 在特定的生物学环境中被认为是相关的，并由糖生物学家命名。在 与蛋白质结构域相似的方式，这些重复的结构基序会会议特定的结合和功能 对包含它们的聚糖结构的活动。这些聚糖图案的许多集合和目录都有 是开发的，但它们是主要列表 - 几乎没有功能理解。 提供生物学背景的资源，以理解主题在细胞中的作用。 glycomotif数据 - 在爱德华兹实验室中开发的资源是为了支持Glygen Glycan知识库，这是一个共同的 资金赞助的数据资源是类似聚糖图案的目录之一，能够注释每个图案 带有名称，关键字和出版物的主题。尽管我们对聚糖的理解相对缺乏 但是，结构图案的功能，我们确实了解负责的糖基化酶机制 用于组装和将聚糖固定到糖蛋白上，并可以枚举，尽管数据资源 由Glygen提供的，固定和组装成熟聚糖结构所需的糖酶 在小鼠和人类蛋白质上。我们试图探索糖基果糖的功能注释的实用性 通过基于基因的表型的整合，组织 - 位置和细胞类型注释的图案 来自国际小鼠表型联盟和GTEX COMMON的相关糖酶 与glycomotif进行资金数据研究，从而为全面功能提供了一个平台 聚糖基序的注释，以及最终在Glygen中的聚糖结构。