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

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• 作者：Scott R. Kronewitter ; Gordon W. Slysz ; Ioan Marginean ; Clay D. Hagler ; Brian L. LaMarche ; Rui Zhao ; Myanna Y. Harris ; Matthew E. Monroe ; Christina A. Polyukh ; Kevin L. Crowell ; Thomas L. Fillmore ; Timothy S. Carlson ; David G. Camp ; II ; Ronald J. Moore ; Samuel H. Payne ; Gordon A. Anderson ; Richard D. Smith
• 刊名：Analytical Chemistry
• 出版年：2014
• 出版时间：July 1, 2014
• 年：2014
• 卷：86
• 期：13
• 页码：6268-6276
• 全文大小：354K
• ISSN：1520-6882

文摘

Glycomics quintavariate-informed quantification (GlyQ-IQ) is a biologically guided glycomics analysis tool for identifying N-glycans in liquid chromatography鈥搈ass spectrometry (LC鈥揗S) data. Glycomics LC鈥揗S 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鈥揗S data processing. A priori glycan information about the individual target鈥檚 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鈥揗S detection to improve the specificity of the analysis. The GlyQ-IQ software was developed in this work and evaluated in the context of profiling the N-glycan compositions from human serum LC鈥揗S data sets. A case study is presented to demonstrate how GlyQ-IQ identifies and removes confounding chromatographic peaks from high mannose glycan isomers from human blood serum. In addition, GlyQ-IQ was used to generate a broad human serum N-glycan profile from a high resolution nanoelectrospray-liquid chromatography鈥搕andem mass spectrometry (nESI-LC鈥揗S/MS) data set. A total of 156 glycan compositions and 640 glycan isomers were detected from a single sample. Over 99% of the GlyQ-IQ glycan-feature assignments passed manual validation and are backed with high-resolution mass spectra.