Glycan Substructure Mining Tool: An Updated and Convenient Method Focused on Gut and Pathogenic Microbiota for Glycan...

The microbiota serves as a linker between the environment and the human body, with glycans mediating this interaction through structurally distinct domains similar to the domain of proteins. However, the "glycan code" governing structure-function relationships remains underexplored. We developed the Glycan Substructure Mining tool (GSMtool), a graph-based Python framework for systematic identification and comparative analysis of conserved glycan substructures in large-scale microbial data sets. GSMtool identified specific glycan substructures in gut microbiota or pathogenic bacteria, including the subtle differences in Shigella flexneri and diarrhea-associated αDGlcp(1-3)βDGalpNAc epitope. Validation through Helicobacter pylori and Clostridium difficile confirmed the capacity of the GSMtool to identify pathogen-specific diagnostic glycan substructures. The framework integrates two analytical pipelines accommodating diverse research objectives. This methodology advances our understanding of the relationship between glycan substructure and its function while identifying potential targets for microbial diagnostics and carbohydrate-based vaccine development.