Comparative Analysis and Validation of Different Steps in Glycomics Studies

Methods Enzymol. 2017:586:37-55. doi: 10.1016/bs.mie.2016.09.027. Epub 2016 Oct 24.

Abstract

Large-scale glycomics studies enable identification of aberrant glycosylation patterns in disease and provide information about functional relevance of individual glycans through genome-wide association studies. Developed high-throughput methodologies have to be sensitive, robust, and stable during long periods of time (few months) to be able to reliably detect small biological variations in glycosylation. Here, we describe a simple, robust, and affordable protocol for immunoglobulin G N-glycan analysis by hydrophilic interaction liquid chromatography-ultra-performance liquid chromatography (HILIC-UPLC), as well as useful strategies for method optimization: Plackett-Burman screening design and analysis of source of variation. We put our focus on experimental design for high-throughput glycan analysis, critical steps in sample preparation procedure for obtaining high-quality data, and propose a validation protocol relevant for high-throughput methods in terms of their long-term robustness and ability to detect biologically relevant changes in glycosylation. The quality of the procedure was assessed by employing appropriate experimental designs and subsequent statistical techniques.

Keywords: Glycans; Glycome analysis; HILIC; High throughput; Method validation; UPLC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid
  • Female
  • Glycomics / methods
  • Glycosylation
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / isolation & purification*
  • Male
  • Protein Processing, Post-Translational*

Substances

  • Immunoglobulin G