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.

摘要 聚糖在细胞-细胞相互作用、细胞信号传导和免疫应答中发挥重要作用，具有特异性的免疫应答。 负责驱动聚糖的细胞和蛋白质结合活性的聚糖结构基序， 功能作用。尽管聚糖具有显著的结构异质性，但这些聚糖基序或决定簇， 被认为与特定的生物学背景相关，并由糖生物学家命名。中 与蛋白质结构域类似，这些重复出现结构基序赋予特异性结合和功能 活性转移到含有它们的聚糖结构上。这些聚糖基序的许多集合和目录具有 但它们主要是列表-这些列表很少或根本没有功能性理解 这些资源为理解基序在细胞中的作用提供了生物学背景。GlycoMotif数据- 资源，在Edwards实验室开发，以支持GlyGen聚糖知识库，一个通用的- 基金赞助的数据资源，就是这样一个聚糖基序目录，具有注释每个 主题与名称，关键字和出版物。尽管我们对聚糖的了解相对较少 结构基序的功能，然而，我们确实了解负责糖基化酶机制 用于组装和连接聚糖糖蛋白，并可以枚举，虽然数据资源 由GlyGen提供，是连接和组装成熟聚糖结构所必需的糖酶 对小鼠和人类蛋白质的影响。我们试图探索GlycoMotif聚糖功能注释的实用性， 通过整合基于基因的表型、组织定位和细胞类型注释， 来自国际小鼠表型鉴定协会和GTEx常见- 基金数据资源与GlycoMotif，从而提供一个平台，全面的功能 GlyGen中聚糖基序的注释，以及最终的聚糖结构。