Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Aging (Albany NY). 2021 Mar 19;13(7):9160-9185. doi: 10.18632/aging.202718.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we collected open access data to analyze the mechanisms associated with SARS-CoV-2 infection. Gene set enrichment analysis (GSEA) revealed that apoptosis-related pathways were enriched in the cells after SARS-CoV-2 infection, and the results of differential expression analysis showed that biological functions related to endoplasmic reticulum stress (ERS) and lipid metabolism were disordered. TMBIM6 was identified as a potential target for SARS-CoV-2 in host cells through weighted gene coexpression network analysis (WGCNA) of the time course of expression of host and viral proteins. The expression and related functions of TMBIM6 were subsequently analyzed to illuminate how viral proteins interfere with the physiological function of host cells. The potential function of viral proteins was further analyzed by GEne Network Inference with Ensemble of trees (GENIE3). This study identified TMBIM6 as a target protein associated with the pathogenesis of SARS-CoV-2, which might provide a novel therapeutic approach for COVID-19 in the future.
2019 年冠状病毒病(COVID-19)由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起。在这项研究中,我们收集了开放获取的数据来分析与 SARS-CoV-2 感染相关的机制。基因集富集分析(GSEA)显示,SARS-CoV-2 感染后与细胞凋亡相关的途径被富集,差异表达分析的结果表明,与内质网应激(ERS)和脂质代谢相关的生物学功能紊乱。通过宿主蛋白和病毒蛋白表达时间过程的加权基因共表达网络分析(WGCNA),鉴定 TMBIM6 是宿主细胞中 SARS-CoV-2 的潜在靶点。随后分析了 TMBIM6 的表达及其相关功能,以阐明病毒蛋白如何干扰宿主细胞的生理功能。通过 Ensemble of trees(GENIE3)的基因网络推断进一步分析了病毒蛋白的潜在功能。本研究鉴定了 TMBIM6 作为与 SARS-CoV-2 发病机制相关的靶蛋白,这可能为未来 COVID-19 的治疗提供新的途径。