Personalized Profiling of Lipoprotein and Lipid Metabolism Based on 1018 Measures from Combined Quantitative NMR and LC-MS/MS Platforms

Abstract

Applications of advanced omics methodologies are increasingly popular in biomedicine. However, large-scale studies aiming at clinical translation are typically siloed to single technologies. Here, we present the first comprehensive large-scale population data combining 209 lipoprotein measures from a quantitative NMR spectroscopy platform and 809 lipid classes and species from a quantitative LC-MS/MS platform. These data with 1018 molecular measures were analyzed in two population cohorts totaling 7830 participants. The association and cluster analyses revealed excellent coherence between the methodologically independent data domains and confirmed their quantitative compatibility and suitability for large-scale studies. The analyses elucidated the detailed molecular characteristics of the heterogeneous circulatory macromolecular lipid transport system and the underlying structural and compositional relationships. Unsupervised neural network analysis─the so-called self-organizing maps (SOMs)─revealed that these deep molecular and metabolic data are inherently related to key physiological and clinical population characteristics. The data-driven population subgroups uncovered marked differences in the population distribution of multiple cardiometabolic risk factors. These include, e.g., multiple lipoprotein lipids, apolipoprotein B, ceramides, and oxidized lipids. All 79 structurally unique triglyceride species showed similar associations over the entire lipoprotein cascade and indicated systematically increased risk for carotid intima media thickening and other atherosclerosis risk factors, including obesity and inflammation. The metabolic attributes for 27 individual cholesteryl ester species, which formed six distinct clusters, were more intricate with associations both with higher─e.g., CE(16:1)─and lower─e.g., CE(20:4)─cardiometabolic risk. The molecular details provided by these combined data are unprecedented for molecular epidemiology and demonstrate a new potential avenue for population studies.