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结合生物信息学和机器学习算法,鉴定和分析 COVID-19 恢复期和糖尿病共有的生物标志物和通路。

Combining bioinformatics and machine learning algorithms to identify and analyze shared biomarkers and pathways in COVID-19 convalescence and diabetes mellitus.

机构信息

The First Clinical Medical School, Harbin Medical University, Harbin, China.

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

出版信息

Front Endocrinol (Lausanne). 2023 Dec 19;14:1306325. doi: 10.3389/fendo.2023.1306325. eCollection 2023.

Abstract

BACKGROUND

Most patients who had coronavirus disease 2019 (COVID-19) fully recovered, but many others experienced acute sequelae or persistent symptoms. It is possible that acute COVID-19 recovery is just the beginning of a chronic condition. Even after COVID-19 recovery, it may lead to the exacerbation of hyperglycemia process or a new onset of diabetes mellitus (DM). In this study, we used a combination of bioinformatics and machine learning algorithms to investigate shared pathways and biomarkers in DM and COVID-19 convalescence.

METHODS

Gene transcriptome datasets of COVID-19 convalescence and diabetes mellitus from Gene Expression Omnibus (GEO) were integrated using bioinformatics methods and differentially expressed genes (DEGs) were found using the R programme. These genes were also subjected to Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to find potential pathways. The hub DEGs genes were then identified by combining protein-protein interaction (PPI) networks and machine learning algorithms. And transcription factors (TFs) and miRNAs were predicted for DM after COVID-19 convalescence. In addition, the inflammatory and immune status of diabetes after COVID-19 convalescence was assessed by single-sample gene set enrichment analysis (ssGSEA).

RESULTS

In this study, we developed genetic diagnostic models for 6 core DEGs beteen type 1 DM (T1DM) and COVID-19 convalescence and 2 core DEGs between type 2 DM (T2DM) and COVID-19 convalescence and demonstrated statistically significant differences (<0.05) and diagnostic validity in the validation set. Analysis of immune cell infiltration suggests that a variety of immune cells may be involved in the development of DM after COVID-19 convalescence.

CONCLUSION

We identified a genetic diagnostic model for COVID-19 convalescence and DM containing 8 core DEGs and constructed a nomogram for the diagnosis of COVID-19 convalescence DM.

摘要

背景

大多数患有 2019 年冠状病毒病(COVID-19)的患者已完全康复,但还有许多其他患者经历了急性后遗症或持续症状。急性 COVID-19 康复可能只是慢性疾病的开始。即使 COVID-19 康复后,它也可能导致高血糖过程恶化或新发糖尿病(DM)。在这项研究中,我们使用生物信息学和机器学习算法的组合来研究 DM 和 COVID-19 恢复期的共享途径和生物标志物。

方法

使用生物信息学方法整合来自基因表达综合数据库(GEO)的 COVID-19 恢复期和糖尿病的基因转录组数据集,并使用 R 程序找到差异表达基因(DEG)。还对这些基因进行了基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)途径分析,以寻找潜在途径。然后,通过结合蛋白质-蛋白质相互作用(PPI)网络和机器学习算法,确定核心 DEG 基因。预测 COVID-19 恢复期后 DM 的转录因子(TF)和 microRNA。此外,通过单样本基因集富集分析(ssGSEA)评估 COVID-19 恢复期后糖尿病的炎症和免疫状态。

结果

在这项研究中,我们开发了 COVID-19 恢复期与 1 型糖尿病(T1DM)和 COVID-19 恢复期与 2 型糖尿病(T2DM)之间的 6 个核心 DEG 之间的遗传诊断模型,并在验证集中证明了统计学差异(<0.05)和诊断有效性。免疫细胞浸润分析表明,多种免疫细胞可能参与 COVID-19 恢复期后 DM 的发生。

结论

我们确定了包含 8 个核心 DEG 的 COVID-19 恢复期和 DM 的遗传诊断模型,并构建了 COVID-19 恢复期 DM 的诊断列线图。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cf1/10758397/5d35595597e9/fendo-14-1306325-g001.jpg

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