In immunoglobulin G (IgG), N-glycosylation plays a pivotal role in structure and function. It is often altered in different diseases, suggesting that it could be a promising health biomarker. Studies indicate that IgG glycosylation not only associates with various diseases but also has predictive capabilities. Additionally, changes in IgG glycosylation correlate with physiological and biochemical traits known to reflect overall health state. This study aimed to investigate the power of IgG glycans to predict physiological and biochemical parameters. We developed two models using IgG N-glycan data as an input: a regression model using elastic net and a machine learning model using deep learning. Data were obtained from the Korčula and Vis cohorts. The Korčula cohort data were used to train both models, while the Vis cohort was used exclusively for validation. Our results demonstrated that IgG glycome composition effectively predicts several biochemical and physiological parameters, especially those related to lipid and glucose metabolism and cardiovascular events. Both models performed similarly on the Korčula cohort; however, the deep learning model showed a higher potential for generalization when validated on the Vis cohort. This study reinforces the idea that IgG glycosylation reflects individuals' health state and brings us one step closer to implementing glycan-based diagnostics in personalized medicine. Additionally, it shows that the predictive power of IgG glycans can be used for imputing missing covariate data in deep learning frameworks.
Keywords: IgG; N-glycosylation; biochemical parameters; cardiometabolic events; deep learning; elastic net; physiological parameters.