Multi-omic profiling of atherosclerosis: protocol and pilot data for the AtherOMICS biobank

Omics technologies enable deep profiling of human atherosclerosis, but have mostly been applied in small studies lacking integration with other data modalities. AtherOMICS is a biobanking project linking multi-omic atherosclerotic plaque phenotyping with blood biobanking, in vivo imaging, and clinical data. Since August 2022, 212 patients scheduled to undergo carotid or femoral endarterectomy at LMU Klinikum (Munich, Germany), have been enrolled (median age 73 years, 30.5% female). Plaques undergo systematic histological characterization of lipid core, calcification, intraplaque hemorrhage, fibrous cap, macrophages, and smooth muscle cells. Single-nuclei RNAseq (n=17) has highlighted macrophages as the dominant intraplaque cell type, whereas paired plaque and plasma affinity-based proteomics (n=88) quantified 2,841 shared proteins showing low plaque-plasma correlation (median ρ=0.10). Cross-modality image integration (histology, ex vivo MRI, in vivo MRI, CTA) proved feasible. Taken together, AtherOMICS enables multimodal characterization of human atherosclerosis aiming for the discovery of athero-specific drug targets, molecular signatures of atheroprogression, and non-invasive biomarkers of plaque vulnerability.