Derivation and external validation of mass spectrometry-based proteomic model using machine learning algorithms to predict plaque rupture in patients with acute coronary syndrome

IF 3.2 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
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引用次数: 0

Abstract

Background

A poor prognosis is associated with atherosclerotic plaque rupture (PR) despite after conventional therapy for patients with acute coronary syndrome (ACS). Timely identification of PR improves the risk stratification and prognosis of ACS patients.

Methods

A derivation cohort of 110 patients with ACS who underwent pre-intervention optical coherence tomography (OCT) were matched 1:1 to the PR and intact fibrous cap (IFC) groups according to traditional risk factors. Candidate PR proteins were identified via mass spectrometry (MS)-based proteomics using unbiased machine learning methods and were further validated by enzyme-linked immunosorbent assay (ELISA) in an external validation cohort of 85 patients with ACS. The performance of candidate biomakers was assessed using the receiver operating characteristic curve analysis.

Results

1121 proteins were identified and 535 filtered proteins were used for analysis. Nine candidate proteins were screened by five machine learning algorithms. Three proteins (APOC3, RAB39A, and KNG1) were significantly different between the PR and IFC in validation cohort. The performance of plasm APOC3, RAB39A, and KNG1 for differentiating PR and IFC was superior to that of the conventional biomarkers and risk factors.

Conclusion

The proteins (APOC3, RAB39A, and KNG1) serve as a potential novel diagnostic tool to identify PR in ACS patients.

利用机器学习算法推导和外部验证基于质谱的蛋白质组模型,以预测急性冠状动脉综合征患者的斑块破裂。
背景:急性冠状动脉综合征(ACS)患者尽管接受了常规治疗,但动脉粥样硬化斑块破裂(PR)与不良预后有关。及时发现斑块破裂可改善急性冠状动脉综合征患者的风险分层和预后:方法:根据传统的风险因素,将 110 名接受干预前光学相干断层扫描(OCT)的急性冠状动脉综合征(ACS)患者按 1:1 的比例分为 PR 组和完整纤维帽(IFC)组。利用无偏见的机器学习方法,通过基于质谱(MS)的蛋白质组学确定了候选 PR 蛋白,并在由 85 名 ACS 患者组成的外部验证队列中通过酶联免疫吸附试验(ELISA)进行了进一步验证。使用接收器操作特征曲线分析评估了候选生物标记物的性能:结果:共鉴定出 1121 种蛋白质,535 种过滤蛋白质被用于分析。五种机器学习算法筛选出九种候选蛋白质。在验证队列中,三个蛋白质(APOC3、RAB39A和KNG1)在PR和IFC之间存在显著差异。质 APOC3、RAB39A 和 KNG1 在区分 PR 和 IFC 方面的表现优于传统的生物标志物和风险因素:结论:蛋白(APOC3、RAB39A 和 KNG1)是一种潜在的新型诊断工具,可用于鉴别 ACS 患者的 PR。
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来源期刊
Clinica Chimica Acta
Clinica Chimica Acta 医学-医学实验技术
CiteScore
10.10
自引率
2.00%
发文量
1268
审稿时长
23 days
期刊介绍: The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.
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