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机器学习和生物信息学鉴定扩张型心肌病中 8 个自噬相关生物标志物并构建基因调控网络。

Machine learning and bioinformatics to identify 8 autophagy-related biomarkers and construct gene regulatory networks in dilated cardiomyopathy.

机构信息

College of Acupuncture and Massage, Shandong University of Traditional Chinese Medicine, Jinan, China.

College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Sci Rep. 2022 Sep 2;12(1):15030. doi: 10.1038/s41598-022-19027-5.

DOI:10.1038/s41598-022-19027-5
PMID:36056063
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9440113/
Abstract

Dilated cardiomyopathy (DCM) is a condition of impaired ventricular remodeling and systolic diastole that is often complicated by arrhythmias and heart failure with a poor prognosis. This study attempted to identify autophagy-related genes (ARGs) with diagnostic biomarkers of DCM using machine learning and bioinformatics approaches. Differential analysis of whole gene microarray data of DCM from the Gene Expression Omnibus (GEO) database was performed using the NetworkAnalyst 3.0 platform. Differentially expressed genes (DEGs) matching (|log2FoldChange ≥ 0.8, p value < 0.05|) were obtained in the GSE4172 dataset by merging ARGs from the autophagy gene libraries, HADb and HAMdb, to obtain autophagy-related differentially expressed genes (AR-DEGs) in DCM. The correlation analysis of AR-DEGs and their visualization were performed using R language. Gene Ontology (GO) enrichment analysis and combined multi-database pathway analysis were served by the Enrichr online enrichment analysis platform. We used machine learning to screen the diagnostic biomarkers of DCM. The transcription factors gene regulatory network was constructed by the JASPAR database of the NetworkAnalyst 3.0 platform. We also used the drug Signatures database (DSigDB) drug database of the Enrichr platform to screen the gene target drugs for DCM. Finally, we used the DisGeNET database to analyze the comorbidities associated with DCM. In the present study, we identified 23 AR-DEGs of DCM. Eight (PLEKHF1, HSPG2, HSF1, TRIM65, DICER1, VDAC1, BAD, TFEB) molecular markers of DCM were obtained by two machine learning algorithms. Transcription factors gene regulatory network was established. Finally, 10 gene-targeted drugs and complications for DCM were identified.

摘要

扩张型心肌病(DCM)是一种心室重构和收缩舒张功能障碍的疾病,常伴有心律失常和心力衰竭,预后不良。本研究试图采用机器学习和生物信息学方法,从基因表达综合数据库(GEO)中找到与扩张型心肌病诊断相关的自噬相关基因(ARGs)生物标志物。利用 NetworkAnalyst 3.0 平台对 GEO 数据库中 DCM 的全基因微阵列数据进行差异分析。通过合并自噬基因文库 HADb 和 HAMdb 中的 ARGs,在 GSE4172 数据集上获得差异表达基因(DEGs),|log2FoldChange≥0.8,p 值<0.05|,从而获得 DCM 中的自噬相关差异表达基因(AR-DEGs)。使用 R 语言进行 AR-DEGs 的相关性分析及其可视化。采用 Enrichr 在线富集分析平台进行基因本体论(GO)富集分析和联合多数据库通路分析。我们使用机器学习来筛选 DCM 的诊断生物标志物。通过 NetworkAnalyst 3.0 平台的 JASPAR 数据库构建转录因子基因调控网络。我们还使用 Enrichr 平台的药物签名数据库(DSigDB)药物数据库筛选 DCM 的基因靶标药物。最后,我们使用 DisGeNET 数据库分析与 DCM 相关的合并症。在本研究中,我们确定了 23 个 DCM 的 AR-DEGs。通过两种机器学习算法,获得了 8 个(PLEKHF1、HSPG2、HSF1、TRIM65、DICER1、VDAC1、BAD、TFEB)DCM 分子标志物。建立了转录因子基因调控网络。最后,确定了 10 种针对 DCM 的基因靶向药物和并发症。

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