Glycan Substructure Mining tool: An updated and convenient method focused on gut and pathogenic microbiota for glycan research

The microbiota links the environment to the human body, with glycans playing a pivotal role in this interaction. However, the underlying “glycan code” remains incompletely deciphered. Similar to the domain of proteins, the function of glycans is also mediated through the “domain” called glycan substructure. Few studies have been previously conducted for the systematic analysis of substructures. Thus, we present the Glycan Substructure Mining tool (GSMtool), a Python-based computational framework employing graph-based modeling algorithms for the systematic identification and analysis of glycan substructures in large-scale datasets. GSMtool identified specific glycan substructures in gut microbiota or pathogenic bacteria, particularly those that exhibit subtle differences in pathogenic bacteria. And the αDGlcp(1-3)βDGalpNAc showed elevation in diarrhea-causing pathogens. Through case studies of Helicobacter pylori and Clostridium difficile infections, the GSMtool successfully pinpointed pathogen-specific substructures with diagnostic potential. To enhance applicability across diverse research scenarios, the framework incorporates two distinct analytical pipelines. This methodology advances our understanding of the relationship between glycan substructure and its function, while the identified glycan substructures offer targets for diagnostic development and vaccine design.