基于 WGCNA 鉴定 COVID-19 的枢纽基因和分子亚型。

Identification of hub genes and molecular subtypes in COVID-19 based on WGCNA.

机构信息

Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, China.

出版信息

Eur Rev Med Pharmacol Sci. 2021 Oct;25(20):6411-6424. doi: 10.26355/eurrev_202110_27015.

DOI:10.26355/eurrev_202110_27015

PMID:34730223

Abstract

OBJECTIVE

The heterogeneity of clinical manifestations and mortality rates in Coronavirus disease 2019 (COVID-19) patients may be related to the existence of molecular subtypes in COVID-19. To improve current management, it is essential to find the hub genes and pathways associated with different COVID-19 subtypes.

MATERIALS AND METHODS

The whole-genome sequencing information (GSE156063, GSE163151) of nasopharyngeal swabs from normal subjects and COVID-19 patients were downloaded from the Gene Expression Omnibus (GEO) database. The molecular subtypes of patients with COVID-19 were classified using the "consistent clustering" method, and the specific genes associated with each subtype were found. Differentially expressed genes (DEGs) were screened between normal subjects and COVID-19 patients; the Weighted gene co-expression network analysis (WGCNA) method was used to find the key module genes of COVID-19 patients. Subtype-specific, differentially expressed and module-related genes were collected and intersected. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out and protein-protein interaction (PPI) networks were generated. The pathways enriched in COVID-19 subtypes were analyzed by gene set variation analysis (GSVA).

RESULTS

Patients with COVID-19 were divided into three subtypes, and there was no significant difference in gender and age distribution between subtypes. 82 differential gene pathways were screened between Subtypes I and II, 131 differential gene pathways were screened between Subtypes I and III, and 107 differential gene pathways were screened between Subtypes II and III. Finally, 44 differentially expressed key genes were screened, including 11 hub genes (RSAD2, IFIT1, MX1, OAS1, OAS2, BST2, IFI27, IFI35, IFI6, IFITM3, STAT2).

CONCLUSIONS

There are significant differences in gene activation and pathway enrichment among different molecular subtypes of COVID-19, which may account for the heterogeneity in clinical presentation and the prognosis of patients.

摘要

目的

新型冠状病毒肺炎（COVID-19）患者临床表现和死亡率的异质性可能与 COVID-19 存在分子亚型有关。为了改进当前的治疗方法，找到与不同 COVID-19 亚型相关的关键基因和途径至关重要。

材料和方法

从基因表达综合数据库（GEO）中下载鼻咽拭子的全基因组测序信息（GSE156063、GSE163151），用于正常人和 COVID-19 患者。使用“一致聚类”方法对 COVID-19 患者进行分子亚型分类，并找到与每个亚型相关的特定基因。筛选正常人和 COVID-19 患者之间的差异表达基因（DEGs）；使用加权基因共表达网络分析（WGCNA）方法找到 COVID-19 患者的关键模块基因。收集并交集亚型特异性、差异表达和模块相关基因。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，并生成蛋白质-蛋白质相互作用（PPI）网络。通过基因集变异分析（GSVA）分析 COVID-19 亚型中富集的通路。

结果

COVID-19 患者分为 3 个亚型，各亚型间的性别和年龄分布无明显差异。亚型 I 和 II 之间筛选出 82 个差异基因通路，亚型 I 和 III 之间筛选出 131 个差异基因通路，亚型 II 和 III 之间筛选出 107 个差异基因通路。最后筛选出 44 个差异表达的关键基因，包括 11 个枢纽基因（RSAD2、IFIT1、MX1、OAS1、OAS2、BST2、IFI27、IFI35、IFI6、IFITM3、STAT2）。