Recent advances in mass spectrometry (MS)-based glycoproteomics in complex biological samples.

Protein glycosylation plays a key role in various biological processes and disease-related pathological progression. Mass spectrometry (MS)-based glycoproteomics is a powerful approach that provides a system-wide profiling of the glycoproteome in a high-throughput manner. There have been numerous significant technological advances in this field, including improved glycopeptide enrichment, hybrid fragmentation techniques, emerging specialized software packages, and effective quantitation strategies, as well as more dedicated workflows. With increasingly sophisticated glycoproteomics tools on hand, researchers have extensively adapted this approach to explore different biological systems both in terms of in-depth glycoproteome profiling and comparative glycoproteome analysis. Quantitative glycoproteomics enables researchers to discover novel glycosylation-based biomarkers in various diseases with potential to offer better sensitivity and specificity for disease diagnosis. In this review, we present recent methodological developments in MS-based glycoproteomics and highlight its utility and applications in answering various questions in complex biological systems.