Further Development And Application Of GlycoMaple:A Tool For Glycosylation Pathway Analysis

Glycan modifications,including N-glycan,O-glycan,and glycosylphosphatidylinositolanchored(GPI-anchored)modification,are crucial for a variety of cellular processes in mammalian cells,such as signal transduction,immune recognition,fertilization process,carcinogenesis,etc.In mammalian cells,more than 50% proteins are modified by glycans,and more than 146 GPI-anchored proteins(GPI-APs),including receptors,ligands,adhesion molecules and enzymes have been identified in human cells.However,the complexity of the glycosylation pathways in mammalian cells and the lack of comprehensive analysis tools for studying these pathways have made it challenging to fully understand the glycosylation process.Therefore,a clear and concise visualization and analysis tool for glycosylation pathways in cells is of great significance for studying glycosylation and developing new diagnostic and therapeutic targets for various diseases.In previous study,Huang et al.developed Glyco Maple,a high-throughput sequencingbased glycosylation pathway visualization and analysis tool.Here,we optimized Glyco Maple and developed a mouse version of the tool to analyze glycosylation pathways in mouse cells.We also analyzed the GPI-AP related genes expression pattern by using human version Glyco Maple and other analysis tools.The main results were as follows:(1)In total,we created a dataset of 935 mouse genes related to glycans and used it to generate 20 glycosylation pathway maps for mouse cells.Then,based on the human version Glyco Maple,using similar front-end framework and new back-end framework,the mouse Glyco Maple website was built.(2)The visualization and analysis of the glycosylation pathways in both embryonic stem cells and epiblast-like cells which utilized the mouse Glyco Maple website tool revealed significant differences in the expression levels of various genes involved in different glycosylation pathways.Notably,more than half of the genes in the sugar nucleotide biosynthesis pathway exhibited differences in expression levels.(3)Then,our analysis of GPI-AP related gene expression patterns using human version Glyco Maple yielded several key findings.We observed upregulation of the GPI-AP biosynthesis gene PIGY and GPI-AP encoding gene CD14 in lower grade glioma,glioblastoma multiforme,pancreatic cancer,testicular germ cell carcinoma,primary cutaneous melanoma,and metastatic cutaneous melanoma.Moreover,we found that patients with lower grade glioma who exhibited higher expression levels of PIGY and CD14 had shorter overall survival times.We also investigated the expression patterns of GPI-AP encoding genes in normal and cancerous tissues,and identified GAS1,GPC2,and GPC4 as potential biomarkers for lower grade glioma and glioblastoma multiforme.