Comprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity
Fig 2
Lectin binding site features have significant associations with the presence of specific glycans.
Volcano plots show that a substantial proportion of features from all three categories are statistically significantly (q < 0.01) enriched (x > 0) and depleted (x < 0) in interaction characterizations for each of the 15 glycans of interest when compared to background interaction characterizations from all other glycans. It is apparent that pocket-size-correlated D2 distribution & pocket descriptor features (represented by the two lightest blue colored points) are generally enriched for larger glycan ligands (terminal NeuAc, high mannose, 3’-siayllactose) and depleted for interactions with smaller ligands (monosaccharide glycans). Some glycan-lectin interactions have fewer features that are strongly enriched (terminal fucose, N-acetyllactosamine, and TF antigen), possibly indicating a diversity of interaction mechanisms, or that more common, highly similar glycans in the background are reducing the strength of associations. Significance and direction of association was determined by weighted Wilcoxon-Mann-Whitney (WMW) tests accounting for homologous and redundant lectin structures. The x-axis shows the direction and strength of rank-based enrichment for each feature compared to background. The y-axis indicates the statistical significance (q-values) adjusted by the Benjamini-Hochberg procedure applied separately for each ligand with a significance threshold set for an FDR of 0.01 (represented by the solid horizontal lines). Q-values more significant than 1 × 10−16(horizontal dotted line) were scattered between 3 × 10−19 and 1 × 10−16. The vertical line (x = 0) divides positive (right) and negative (left) associations. Glycan symbols follow the SNFG system.