Delineating Diseases by IMS-MS Profiling of Serum N-linked Glycans

Abstract

Altered branching and aberrant expression of N-linked glycans is known to be associated with disease states such as cancer. However, the complexity of determining such variations hinders the development of specific glycomic approaches for assessing disease states. Here, we examine a combination of ion mobility spectrometry (IMS) and mass spectrometry (MS) measurements, with principal component analysis (PCA) for characterizing serum N-linked glycans from 81 individuals: 28 with cirrhosis of the liver; 25 with liver cancer; and 28 apparently healthy. Supervised PCA of combined ion-mobility profiles for several, to as many as ten different mass-to-charge ratios for glycan ions, improves the delineation of diseased states. This extends an earlier study [J.Proteome Res. 2008, 7, 1109-1117] of isomers associated with a single glycan (S1H5N4) in which PCA analysis of the IMS profiles appeared to differentiate the liver cancer group from the other samples. Although performed on a limited number of test subjects, the combination of IMS-MS for different combinations of ions and multivariate PCA analysis shows promise for characterizing disease states.

Glycopeptide Site Heterogeneity and Structural Diversity Determined by Combined Lectin Affinity Chromatography/IMS/CID/MS Techniques

“…Such additional information may be useful in reducing the total workload for MS/MS analysis that is typically used to identify or discover glycopeptides in a compex mixture. Additionally, IMS based platforms allow delineation of isomeric glycan/glycopeptide profiles, which often vary in different physiological and disease states [77]; thus, these approaches may assist efforts in discovering and validating biomarkers in a glycome or glycoproteome.…”

Populations of Metal-Glycan Structures Influence MS Fragmentation Patterns

“…48–56 The IMS-(IMS-)MS analysis in this work is performed on a home-built instrument that has been described previously. 43,57,58 The details regarding different instrumentation components and modes of operations are reported elsewhere 42,59 and only a brief description is provided here. The instrument is comprised of an electrospray source, a 183 cm long drift tube, and a time-of-flight mass analyzer.…”

Intact glycopeptide characterization using mass spectrometry

“…Furthermore, glycan isomers with different linkage or branching styles showed different drift time patterns, which provided insightful information to resolve glycan structures[65]. With the development of IMS technique and availability of commercialized instruments, IMS application for carbohydrate isomers separation and glycan structure characterization is increasing significantly [64–71]. However, the software development for IMS data analysis is currently behind the instrument development, which hinders the application and utilization of IMS.…”