Glycan motifs are the standard readout of comparative glycomics, and pipelines treat them as independent features. Here, we show they are not. Motifs are partially ordered by substructure containment, so a parent motif's abundance dominates each of its children. We make that order explicit as a directed acyclic graph, which stratifies the multiple-testing family correctly and, together with an empirical-Bayes variance prior taken from each motif's containment neighborhood, raises estimated true positives across 45 glycomics datasets from 300 to 442 (+47%, p = 0.0001) after controlling for permutation-null false positives. Because a parent's children and its residual form a genuine sub-composition, their logratio balances need no reference frame and no scale model, and they separate a motif's own change from one inherited from its contexts. Of 337 significant parent motifs, 150 (45%) thus carry no signal of their own, while 138 motifs move only in the decomposition. We present case studies for both glycomics and glycoproteomics, including a recurrent reapportioning of core-1 sialylation at the immune-inhibitory disialyl-T antigen across eight human O-glycomes, and a colorectal fucosylation shift confined to the antenna, neither of which any marginal analysis reports.
Zhao, X., Bojar, D.
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