Atherosclerotic plaque vulnerability quantification system for clinical and biological interpretability
Ge Zhang,
Xiaolin Cui,
Zhen Qin,
Zeyu Wang,
Yongzheng Lu,
Yanyan Xu,
Shuai Xu,
Laiyi Tang,
Li Zhang,
Gangqiong Liu,
Xiaofang Wang,
Jinying Zhang,
Junnan Tang
Affiliations
Ge Zhang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China; Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
Xiaolin Cui
School of Medicine, The Chinese University of Hong Kong (Shenzhen), Shenzhen 518172, China
Zhen Qin
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China; Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
Zeyu Wang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China; Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
Yongzheng Lu
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China; Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
Yanyan Xu
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China; Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
Shuai Xu
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China; Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
Laiyi Tang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China; Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
Li Zhang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China; Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
Gangqiong Liu
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China; Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
Xiaofang Wang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China; Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
Jinying Zhang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China; Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China; Corresponding author
Junnan Tang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China; Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China; Corresponding author
Summary: Acute myocardial infarction dominates coronary artery disease mortality. Identifying bio-signatures for plaque destabilization and rupture is important for preventing the transition from coronary stability to instability and the occurrence of thrombosis events. This computational systems biology study enrolled 2,235 samples from 22 independent bulks cohorts and 14 samples from two single-cell cohorts. A machine-learning integrative program containing nine learners was developed to generate a warning classifier linked to atherosclerotic plaque vulnerability signature (APVS). The classifier displays the reliable performance and robustness for distinguishing ST-elevation myocardial infarction from chronic coronary syndrome at presentation, and revealed higher accuracy to 33 pathogenic biomarkers. We also developed an APVS-based quantification system (APVSLevel) for comprehensively quantifying atherosclerotic plaque vulnerability, empowering early-warning capabilities, and accurate assessment of atherosclerosis severity. It unraveled the multidimensional dysregulated mechanisms at high resolution. This study provides a potential tool for macro-level differential diagnosis and evaluation of subtle genetic pathological changes in atherosclerosis.
