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利用机器学习识别心房颤动中风的蛋白质组学和代谢组学特征。

Using machine learning to identify proteomic and metabolomic signatures of stroke in atrial fibrillation.

机构信息

NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.

Beidahuang Industry Group General Hospital, Harbin, 150001, China.

出版信息

Comput Biol Med. 2024 May;173:108375. doi: 10.1016/j.compbiomed.2024.108375. Epub 2024 Mar 26.

Abstract

Atrial fibrillation (AF) is a common cardiac arrhythmia, with stroke being its most detrimental comorbidity. The exact mechanism of AF related stroke (AFS) still needs to be explored. In this study, we integrated proteomics and metabolomics platform to explore disordered plasma proteins and metabolites between AF patients and AFS patients. There were 22 up-regulated and 31 down-regulated differentially expressed proteins (DEPs) in AFS plasma samples. Moreover, 63 up-regulated and 51 down-regulated differentially expressed metabolites (DEMs) were discovered in AFS plasma samples. We integrated proteomics and metabolomics based on the topological interactions of DEPs and DEMs, which yielded revealed several related pathways such as arachidonic acid metabolism, serotonergic synapse, purine metabolism, tyrosine metabolism and steroid hormone biosynthesis. We then performed a machine learning model to identify potential biomarkers of stroke in AF. Finally, we selected 6 proteins and 6 metabolites as candidate biomarkers for predicting stroke in AF by random forest, the area under the curve being 0.976. In conclusion, this study provides new perspectives for understanding the progressive mechanisms of AF related stroke and discovering innovative biomarkers for determining the prognosis of stroke in AF.

摘要

心房颤动(AF)是一种常见的心律失常,其最有害的合并症是中风。AF 相关中风(AFS)的确切机制仍需探索。在这项研究中,我们整合了蛋白质组学和代谢组学平台,以探索 AF 患者和 AFS 患者之间紊乱的血浆蛋白和代谢物。AFS 血浆样本中有 22 个上调和 31 个下调的差异表达蛋白(DEPs)。此外,在 AFS 血浆样本中还发现了 63 个上调和 51 个下调的差异表达代谢物(DEMs)。我们基于 DEPs 和 DEMs 的拓扑相互作用整合了蛋白质组学和代谢组学,揭示了几个相关途径,如花生四烯酸代谢、血清素能突触、嘌呤代谢、酪氨酸代谢和类固醇激素生物合成。然后,我们进行了机器学习模型以识别 AF 中中风的潜在生物标志物。最后,我们通过随机森林选择了 6 种蛋白质和 6 种代谢物作为预测 AF 中风的候选生物标志物,曲线下面积为 0.976。总之,本研究为理解 AF 相关中风的进展机制提供了新的视角,并为确定 AF 中风的预后提供了创新的生物标志物。

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