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新型冠状病毒感染与2型糖尿病共病联系的生物信息学分析

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本文基于转录组数据研究了新型冠状病毒感染(Coronavirus disease 2019,COVID-19)和2型糖尿病(Type 2 diabetes,T2D)的相互作用机制,寻找疾病的潜在功能模块,为其治疗提供新思路.本文收集了来自GEO(Gene expression omnibus)数据库的10个COVID-19和T2D基因表达谱数据集,并按照4∶6的比例分为训练集和验证集,并进行差异表达基因(Differential expression genes,DEGs)的富集分析和构建蛋白质相互作用(Protein-protein interaction,PPI)网络进行模块化分析,找到了与COVID-19和T2D最紧密相关的关键基因和蛋白质特征模块.基于各组织的DEGs交集结果,本文发现43个共有DEGs,并确定了 5个关键基因(HSP90AA1、SRC、EGFR、MAPK3、CDK1),其中CDK1表现出最高的网络连接性.通过XGBoost等6种机器学习算法进行性能检验显示了关键基因对诊断COVID-19和T2D的潜在价值,并通过qPCR实验证实了关键基因在COVID-19患者和正常对照组PBMC中的表达差异.此外,本文基于模块划分算法得到了 PPI网络的6个潜在功能模块,这些模块主要与糖类、脂类代谢和细胞复制相关联.最后,本文建立了 miRNA-TF-mRNA调控网络,并筛选出TP53和NFIC作为调节共有基因转录的枢纽转录因子(Transcription factor,TF).总之,本文分析了 COVID-19和T2D之间共有的表达特征、生物学通路和调控因子,并探索了基因在转录和翻译中的复杂相互作用,为未来COVID-19和T2D的治疗提供了新思路.
Analysis of the Comorbidity and Biological Mechanism Between COVID-19 and Type 2 Diabetes
This article investigates the interaction mechanism between coronavirus disease 2019(COVID-19)and type 2 diabetes(T2D)using transcriptome data,and aiming to identify potential functional modules for the treatment of these diseases.The study collected 10 gene expression profiles datasets from the Gene Expression Omnibus(GEO)database,divided them into training and validation sets in a 4∶6 ratio and enrichment analysis of differentially expressed genes(DEGs)and modular analysis of protein-protein interactions(PPI)were conducted to identify Key genes and protein modules related to COVID-19 and T2D.43 shared DEGs across tissues were found,and 5 Key genes(HSP90AA1,SRC,EGFR,MAPK3,CDK1)were identified,with CDK1 exhibiting the highest network connectivity.Performance evaluation using six machine learning algorithms,including XGBoost,revealed the potential value of Key genes in diagnosing COVID-19 and T2D.Experimental validation through qPCR confirmed the expression differences of these Key genes in the PBMCs of COVID-19 patients and the normal control group.Additionally,the study identified six potential functional modules of the PPI network using a module partitioning algorithm,which were mainly associated with carbohydrate and lipid metabolism and cell replication.Finally,the study established a miRNA-TF-mRNA regulatory network and identified TP53 and NFIC as hub transcription factors regulating the transcription of shared genes.Overall,this study analyzed the shared expression characteristics,biological pathways,and regulatory factors between COVID-19 and T2D,and explored the complex interactions between genes in transcription and translation,providing new ideas for the treatment of these diseases in the future.

Computational BiologyCOVID-19Diabetes Mellitus,Type 2TranscriptomeInflammation

黄泰、于琦、穆俊芳、刘格良、薛丹阳、陈浩然、常敏静、贺培风

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山西医科大学临床决策研究大数据山西省重点实验室,晋中 030600

山西医科大学基础医学院,晋中 030600

山西医科大学管理学院,晋中 030600

生物信息学 新冠疫情 二型糖尿病 基因表达谱 炎症

国家社会科学基金山西省重点研发计划太原市科技计划校级博士启动基金

21BTQ050202102130501003XG2020-5-06XD2138

2024

病毒学报
中国微生物学会

病毒学报

CSTPCD北大核心
影响因子:1.046
ISSN:1000-8721
年,卷(期):2024.40(1)
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