Deep-Learning Resources for Studying Glycan-Mediated Host-Microbe Interactions

Glycans, the most diverse biopolymer, are shaped by evolutionary pressures stemming from host-microbe interactions. Here, we present machine learning and bioinformatics methods to leverage the evolutionary information present in glycans to gain insights into how pathogens and commensals interact with hosts. By using techniques from natural language processing, we develop deep-learning models for glycans that are trained on a curated dataset of 19,299 unique glycans and can be used to study and predict glycan functions. We show that these models can be utilized to predict glycan immunogenicity and the pathogenicity of bacterial strains, as well as investigate glycan-mediated immune evasion via molecular mimicry. We also develop glycan-alignment methods and use these to analyze virulence-determining glycan motifs in the capsular polysaccharides of bacterial pathogens. These resources enable one to identify and study glycan motifs involved in immunogenicity, pathogenicity, molecular mimicry, and immune evasion, expanding our understanding of host-microbe interactions.