Functional Annotation of Glycan Motifs using Common-Fund Data Resources

点击翻译按钮获取中文摘要

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.