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整合加权基因共表达网络分析(WGCNA)和蛋白质-蛋白质相互作用(PPI)网络以筛选婴儿血管瘤的枢纽基因特征

Integrated WGCNA and PPI Network to Screen Hub Genes Signatures for Infantile Hemangioma.

作者信息

Xu Miao, Ouyang Tianxiang, Lv Kaiyang, Ma Xiaorong

机构信息

Department of Plastic and Reconstructive Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Front Genet. 2021 Jan 15;11:614195. doi: 10.3389/fgene.2020.614195. eCollection 2020.

Abstract

BACKGROUND

Infantile hemangioma (IH) is characterized by proliferation and regression.

METHODS

Based on the GSE127487 dataset, the differentially expressed genes (DEGs) between 6, 12, or 24 months and normal samples were screened, respectively. STEM software was used to screen the continued up-regulated or down-regulated in common genes. The modules were assessed by weighted gene co-expression network analysis (WGCNA). The enrichment analysis was performed to identified the biological function of important module genes. The area under curve (AUC) value and protein-protein interaction (PPI) network were used to identify hub genes. The differential expression of hub genes in IH and normal tissues was detected by qPCR.

RESULTS

There were 5,785, 4,712, and 2,149 DEGs between 6, 12, and 24 months and normal tissues. We found 1,218 DEGs were up-regulated or down-regulated expression simultaneously in common genes. They were identified as 10 co-expression modules. Module 3 and module 4 were positively or negatively correlated with the development of IH, respectively. These two module genes were significantly involved in immunity, cell cycle arrest and mTOR signaling pathway. The two module genes with AUC greater than 0.8 at different stages of IH were put into PPI network, and five genes with the highest degree were identified as hub genes. The differential expression of these genes was also verified by qRTPCR.

CONCLUSION

Five hub genes may distinguish for proliferative and regressive IH lesions. The WGCNA and PPI network analyses may help to clarify the molecular mechanism of IH at different stages.

摘要

背景

婴儿血管瘤(IH)具有增殖和消退的特征。

方法

基于GSE127487数据集,分别筛选6个月、12个月或24个月样本与正常样本之间的差异表达基因(DEG)。使用STEM软件筛选共同基因中持续上调或下调的基因。通过加权基因共表达网络分析(WGCNA)评估模块。进行富集分析以确定重要模块基因的生物学功能。使用曲线下面积(AUC)值和蛋白质-蛋白质相互作用(PPI)网络来识别枢纽基因。通过qPCR检测枢纽基因在IH和正常组织中的差异表达。

结果

6个月、12个月和24个月样本与正常组织之间分别有5785个、4712个和2149个DEG。我们发现1218个DEG在共同基因中同时上调或下调表达。它们被鉴定为10个共表达模块。模块3和模块4分别与IH的发展呈正相关或负相关。这两个模块基因显著参与免疫、细胞周期停滞和mTOR信号通路。将在IH不同阶段AUC大于0.8的两个模块基因放入PPI网络,鉴定出5个度数最高的基因作为枢纽基因。这些基因的差异表达也通过qRTPCR得到验证。

结论

五个枢纽基因可能区分增殖性和消退性IH病变。WGCNA和PPI网络分析可能有助于阐明IH不同阶段的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d0c/7844399/2f766b48900a/fgene-11-614195-g001.jpg

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