Abstract
Glycans are complex, yet ubiquitous across biological systems. They are involved in diverse essential organismal functions. Aberrant glycosylation may lead to disease development, such as cancer, autoimmune diseases, and inflammatory diseases. Glycans, both normal and aberrant, are synthesized using extensive glycosylation machinery, and understanding this machinery can provide invaluable insights for diagnosis, prognosis, and treatment of various diseases. Increasing amounts of glycomics data are being generated thanks to advances in glycoanalytics technologies, but to maximize the value of such data, innovations are needed for analyzing and interpreting large-scale glycomics data. Artificial intelligence (AI) provides a powerful analysis toolbox in many scientific fields, and here we review state-of-the-art AI approaches on glycosylation analysis. We further discuss how models can be analyzed to gain mechanistic insights into glycosylation machinery and how the machinery shapes glycans under different scenarios. Finally, we propose how to leverage the gained knowledge for developing predictive AI-based models of glycosylation. Thus, guiding future research of AI-based glycosylation model development will provide valuable insights into glycosylation and glycan machinery.