A computational approach to characterizing bond linkages of glycan isomers using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry.

Glycans commonly exhibit variations in their branching structures and glycosidic bond linkages, in addition to their sequence variation. These glycan features are known to be highly correlated with their biological functions. It is relatively straightforward to deduce the composition and sequence of monosaccharides of a glycan from its tandem mass spectra. However, the characterization of the linkage types of each glycosidic bond is still analytically challenging. In this paper, we present a rank-based discriminative model to differentiate between two types of glycosidic linkages (namely, 1-4 and 1-6) based on the cross-ring fragmentation patterns of the corresponding glycans observed under high-energy collision-induced dissociation (CID). To train our models, we acquired tandem mass spectra for three groups of both native and permethylated linear oligoglucoses using a matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI/TOF/TOF) instrument. Based on a 5-fold cross-validation, the prediction accuracies of our model for native glycans are determined to be about 88.4% and 92.9% for 1-6 and 1-4 linkages, respectively. The accuracies determined for permethylated glycans are slightly lower, but comparable: 85.6% and 89.0% for 1-6 and 1-4 linkages, respectively. Our method is implemented as a web-hosted utility, thus making it readily accessible to the public which can be accessed through http://ggdb.informatics.indiana.edu:8080/glycanview.