An integrated platform for mucin-type O-glycosylation network generation and visualization

Mucin-type O-glycans have profound effects on the structure and stability of glycoproteins. O-Glycans on the cell surface proteins also modulate the cell's interactions with the surrounding environments and other cells. The synthetic pathway of O-glycans involves a large number of enzymes with diverse substrate specificity. The expression pattern of these enzymes is cell and tissue-specific, thus making the pathway highly diverse. To facilitate pathway analysis in a cell and tissue-specific fashion, we developed an integrated platform of RING (Rule Input Network Generator) and O-GlycoVis. RING uses an English-like reaction language to describe the substrate specificity of enzymes and additional constraints on the formation of the glycan products. Using this information, the RING generates a list of possible glycans, which is used as input into O-Glycovis. O-GlycoVis displays the glycan distribution in the pathway and potential reaction paths leading to each glycan. With the input glycan data, O-GlycoVis also traces all possible reaction paths leading to each glycan and outputs pathway maps with the relative abundance levels of glycans overlaid. O-Glycan profiles from two breast cancer cell lines, MCF7 and T47d, human umbilical vascular endothelium cells, Chinese Hamster Ovary cells were generated based on transcriptional data and compared with experimentally observed O-glycans. This RING-based program allows rules to be added or subtracted for network generation and visualization of networks of O-glycosylation network of different tissues and species.