GlyQ-IQ: Glycomics Quintavariate-Informed Quantificationwith High-Performance Computing and GlycoGrid 4D Visualization

摘要

Glycomics quintavariate-informed quantification (GlyQ-IQ) is a biologically guided glycomics analysis tool for identifying N-glycans in liquid chromatography–mass spectrometry (LC–MS) data. Glycomics LC–MS data sets have convoluted extracted ion chromatograms that are challenging to deconvolve with existing software tools. LC deconvolution into constituent pieces is critical in glycomics data sets because chromatographic peaks correspond to different intact glycan structural isomers. The biological targeted analysis approach offers several key advantages to traditional LC–MS data processing. A priori glycan information about the individual target’s elemental composition allows for improved sensitivity by utilizing the exact isotope profile information to focus chromatogram generation and LC peak fitting on the isotopic species having the highest intensity. Glycan target annotation utilizes glycan family relationships and in source fragmentation in addition to high specificity feature LC–MS detection to improve the specificity of the analysis. The GlyQ-IQ software was developed in this work and evaluated in the context ofprofiling the N-glycan compositions from human serum LC–MSdata sets. A case study is presented to demonstrate how GlyQ-IQ identifiesand removes confounding chromatographic peaks from high mannose glycanisomers from human blood serum. In addition, GlyQ-IQ was used to generatea broad human serum N-glycan profile from a high resolution nanoelectrospray-liquidchromatography–tandem mass spectrometry (nESI-LC–MS/MS)data set. A total of 156 glycan compositions and 640 glycan isomerswere detected from a single sample. Over 99% of the GlyQ-IQ glycan-featureassignments passed manual validation and are backed with high-resolutionmass spectra.