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利用脂质组学结合机器学习早期识别伴有急诊胸痛的ST段抬高型心肌梗死患者

Early identification of STEMI patients with emergency chest pain using lipidomics combined with machine learning.

作者信息

Shang Zhi, Liu Yang, Yuan Yu-Yao, Wang Xin-Yu, Yu Hai-Yi, Gao Wei

机构信息

Department of Cardiology, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.

Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing, China.

出版信息

J Geriatr Cardiol. 2022 Sep 28;19(9):685-695. doi: 10.11909/j.issn.1671-5411.2022.09.003.

Abstract

OBJECTIVES

To analyze the differential expression of lipid spectrum between ST-segment elevated myocardial infarction (STEMI) and patients with emergency chest pain and excluded coronary artery disease (CAD), and establish the predictive model which could predict STEMI in the early stage.

METHODS

We conducted a single-center, nested case-control study using the emergency chest pain cohort of Peking University Third Hospital. Untargeted lipidomics were conducted while LASSO regression as well as XGBoost combined with greedy algorithm were used to select lipid molecules.

RESULTS

Fifty-two STEMI patients along with 52 controls were enrolled. A total of 1925 lipid molecules were detected. There were 93 lipid molecules in the positive ion mode which were differentially expressed between the STEMI and the control group, while in the negative ion mode, there were 73 differentially expressed lipid molecules. In the positive ion mode, the differentially expressed lipid subclasses were mainly diacylglycerol (DG), lysophophatidylcholine (LPC), acylcarnitine (CAR), lysophosphatidyl ethanolamine (LPE), and phosphatidylcholine (PC), while in the negative ion mode, significantly expressed lipid subclasses were mainly free fatty acid (FA), LPE, PC, phosphatidylethanolamine (PE), and phosphatidylinositol (PI). LASSO regression selected 22 lipids while XGBoost combined with greedy algorithm selected 10 lipids. PC (15: 0/18: 2), PI (19: 4), and LPI (20: 3) were the overlapping lipid molecules selected by the two feature screening methods. Logistic model established using the three lipids had excellent performance in discrimination and calibration both in the derivation set (AUC: 0.972) and an internal validation set (AUC: 0.967). In 19 STEMI patients with normal cardiac troponin, 18 patients were correctly diagnosed using lipid model.

CONCLUSIONS

The differentially expressed lipids were mainly DG, CAR, LPC, LPE, PC, PI, PE, and FA. Using lipid molecules selected by XGBoost combined with greedy algorithm and LASSO regression to establish model could accurately predict STEMI even in the more earlier stage.

摘要

目的

分析ST段抬高型心肌梗死(STEMI)与急诊胸痛且排除冠状动脉疾病(CAD)患者之间血脂谱的差异表达,并建立可早期预测STEMI的预测模型。

方法

我们利用北京大学第三医院的急诊胸痛队列进行了一项单中心巢式病例对照研究。进行非靶向脂质组学分析,同时使用LASSO回归以及结合贪婪算法的XGBoost来选择脂质分子。

结果

纳入了52例STEMI患者和52例对照。共检测到1925种脂质分子。在正离子模式下,STEMI组与对照组之间有93种脂质分子差异表达,而在负离子模式下,有73种差异表达的脂质分子。在正离子模式下,差异表达的脂质亚类主要是二酰基甘油(DG)、溶血磷脂酰胆碱(LPC)、酰基肉碱(CAR)、溶血磷脂酰乙醇胺(LPE)和磷脂酰胆碱(PC),而在负离子模式下,显著表达的脂质亚类主要是游离脂肪酸(FA)、LPE、PC、磷脂酰乙醇胺(PE)和磷脂酰肌醇(PI)。LASSO回归选择了22种脂质,而结合贪婪算法的XGBoost选择了10种脂质。PC(15:0/18:2)、PI(19:4)和LPI(20:3)是两种特征筛选方法共同选择的重叠脂质分子。使用这三种脂质建立的逻辑模型在推导集(AUC:0.972)和内部验证集(AUC:0.967)中的判别和校准性能均优异。在19例心肌肌钙蛋白正常的STEMI患者中,使用脂质模型正确诊断了18例。

结论

差异表达的脂质主要是DG、CAR、LPC、LPE、PC、PI、PE和FA。使用结合贪婪算法的XGBoost和LASSO回归选择的脂质分子建立模型,即使在更早阶段也能准确预测STEMI。

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