Abstract

We first identified Cholesterol homeostasis and NK cell-associated mechanisms in CAD patients with AMI. • We first identified Cholesterol homeostasis and NK cell-associated predictive and therapeutic model for prediction of AMI in CAD patients via AI-driven multi-omic pipelines • We first elucidated NAMPT and CLEC4D molecular and immune patterns in CAD patients with AMI at multi-omic levels Objective Dysregulation of Cholesterol homeostasis(CH) and NK cells proportion can increase risk of ST-Elevated Myocardial Infarction(STEMI) for Coronary atherosclerotic heart disease(CAD) patients. Hence, it is necessary for the investigation of CH and MC in pathogenesis of STEMI for CAD patients, providing additional choice for the prevention of STEMI for CAD patients. Methods By combining 5 peripheral blood bulk profiles of CAD patients with STEMI and integrative bioinformatic pipelines, such as ssGSEA, CIBERSORT, WGCNA, machine learning, consensus clustering, we first identified novel CH and NK cell(NCH)-associated molecular subgroup and hub genes for CAD patients with STEMI, and then estimated hub genes predictive performance for STEMI onset among CAD patients. Besides, the biological features of hub gene were estimated both in bulk and single-cell profiles of CAD patients with STEMI, especially in artificial intelligence(AI)-driven virtual cells. Indeed, AI-empowered therapeutic enrichment framework(DrugRefLector) and molecular docking were cross-performed for identification of optimal preventative agents targeting hub genes for CAD patients. Finally, in vitro study confirmed the differentially expressed level of hub genes. Results Integrated NCH can lead to the molecular stratification for CAD patients with AMI, which provides insights into the patient precision medicine. Besides, NAMPT and CLEC4D can be considered as up-regulated NCH-associated hub gene involved in STEMI pathogenesis of CAD patients with satisfied predictive efficacy, which was mainly distributed at N