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基于生物信息学方法的缺血性卒中循环免疫图谱识别

Identification of circulating immune landscape in ischemic stroke based on bioinformatics methods.

作者信息

Li Danyang, Li Lifang, Quan Fei, Wang Tianfeng, Xu Si, Li Shuang, Tian Kuo, Feng Meng, He Ni, Tian Liting, Chen Biying, Zhang Huixue, Wang Lihua, Wang Jianjian

机构信息

Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

出版信息

Front Genet. 2022 Jul 25;13:921582. doi: 10.3389/fgene.2022.921582. eCollection 2022.

Abstract

Ischemic stroke (IS) is a high-incidence disease that seriously threatens human life and health. Neuroinflammation and immune responses are key players in the pathophysiological processes of IS. However, the underlying immune mechanisms are not fully understood. In this study, we attempted to identify several immune biomarkers associated with IS. We first retrospectively collected validated human IS immune-related genes (IS-IRGs) as seed genes. Afterward, potential IS-IRGs were discovered by applying random walk with restart on the PPI network and the permutation test as a screening strategy. Doing so, the validated and potential sets of IS-IRGs were merged together as an IS-IRG catalog. Two microarray profiles were subsequently used to explore the expression patterns of the IS-IRG catalog, and only IS-IRGs that were differentially expressed between IS patients and controls in both profiles were retained for biomarker selection by the Random Forest rankings. and were finally identified as immune biomarkers of IS, and a classification model was constructed and verified based on the weights of two biomarkers obtained from the Neural Network algorithm. Furthermore, the CIBERSORT algorithm helped us determine the proportions of circulating immune cells. Correlation analyses between IS immune biomarkers and immune cell proportions demonstrated that was strongly correlated with the proportion of neutrophils (r = 0.72). These results may provide potential targets for further studies on immuno-neuroprotection therapies against reperfusion injury.

摘要

缺血性中风(IS)是一种高发病,严重威胁人类生命健康。神经炎症和免疫反应是IS病理生理过程中的关键因素。然而,其潜在的免疫机制尚未完全明确。在本研究中,我们试图识别几种与IS相关的免疫生物标志物。我们首先回顾性收集经过验证的人类IS免疫相关基因(IS-IRGs)作为种子基因。随后,通过在蛋白质-蛋白质相互作用(PPI)网络上应用带重启的随机游走以及置换检验作为筛选策略来发现潜在的IS-IRGs。通过这种方式,将经过验证的和潜在的IS-IRGs集合合并在一起,形成一个IS-IRG目录。随后使用两个微阵列图谱来探索IS-IRG目录的表达模式,并且仅保留在两个图谱中IS患者和对照之间差异表达的IS-IRGs,以便通过随机森林排名进行生物标志物选择。最终确定 和 为IS的免疫生物标志物,并基于从神经网络算法获得的两种生物标志物的权重构建并验证了一个分类模型。此外,CIBERSORT算法帮助我们确定循环免疫细胞的比例。IS免疫生物标志物与免疫细胞比例之间的相关性分析表明, 与中性粒细胞比例密切相关(r = 0.72)。这些结果可能为进一步研究针对再灌注损伤的免疫神经保护疗法提供潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a8c/9358692/d010d2217c92/fgene-13-921582-g001.jpg

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