GlyCombo Enables Rapid,\nComplete Glycan Composition\nIdentification across Diverse Glycomic Sample Types

Glycans are sugar-based\npolymers found to modify biomolecules,\nincluding lipids and proteins, as well as occur unconjugated as free\npolysaccharides. Due to their ubiquitous cellular presentation, glycans\nmediate crucial biological processes and are frequently sought after\nas biomarkers for a wide range of diseases. Identification of glycans\npresent in samples acquired with mass spectrometry (MS) is a cornerstone\nof glycomics research; thus, the ability to rapidly identify glycans\nin each acquisition is integral to glycomics analysis pipelines. Here\nwe introduce GlyCombo (https://github.com/Protea-Glycosciences/GlyCombo), an open-source, freely available software tool designed to rapidly\nassign monosaccharide combinations to glycan precursor masses including\nthose subjected to MS2 in LC-MS/MS experiments. GlyCombo was evaluated\nacross six diverse data sets, demonstrating MS vendor, derivatization,\nand glycan-type neutrality. Compositional assignments using GlyCombo\nare shown to be faster than the current predominant approach, GlycoMod,\na closed-source web application. Two unique features of GlyCombo,\nmultiple adduct search and off-by-one error anticipation, reduced\nunassigned MS2 scans in a benchmark data set by 40%. Finally, the\ncomprehensiveness of glycan feature identification is exhibited in\nSkyline, a software that requires predefined transitions that are\nderived from GlyCombo output files.