Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle, Germany.
Institute of Pathology, Martin Luther University Halle-Wittenberg, Halle, Germany.
Front Immunol. 2021 Mar 16;12:597399. doi: 10.3389/fimmu.2021.597399. eCollection 2021.
There exists increasing evidence that people with preceding medical conditions, such as diabetes and cancer, have a higher risk of infection with SARS-CoV-2 and are more vulnerable to severe disease. To get insights into the possible role of the immune system upon COVID-19 infection, 2811 genes of the gene ontology term "immune system process GO: 0002376" were selected for coexpression analysis of the human targets of SARS-CoV-2 (HT-SARS-CoV-2) ACE2, TMPRSS2, and FURIN in tissue samples from patients with cancer and diabetes mellitus. The network between HT-SARS-CoV-2 and immune system process genes was analyzed based on functional protein associations using STRING. In addition, STITCH was employed to determine druggable targets. DPP4 was the only immune system process gene, which was coexpressed with the three HT-SARS-CoV-2 genes, while eight other immune genes were at least coexpressed with two HT-SARS-CoV-2 genes. STRING analysis between immune and HT-SARS-CoV-2 genes plotted 19 associations of which there were eight common networking genes in mixed healthy (323) and pan-cancer (11003) tissues in addition to normal (87), cancer (90), and diabetic (128) pancreatic tissues. Using this approach, three commonly applicable druggable connections between HT-SARS-CoV-2 and immune system process genes were identified. These include positive associations of ACE2-DPP4 and TMPRSS2-SRC as well as a negative association of FURIN with ADAM17. Furthermore, 16 drugs were extracted from STITCH (score <0.8) with 32 target genes. Thus, an immunological network associated with HT-SARS-CoV-2 using bioinformatics tools was identified leading to novel therapeutic opportunities for COVID-19.
越来越多的证据表明，患有糖尿病和癌症等先前疾病的人感染 SARS-CoV-2 的风险更高，并且更容易患重病。为了深入了解 COVID-19 感染时免疫系统的可能作用，选择了基因本体术语“免疫系统过程 GO：0002376”的 2811 个基因，用于对癌症和糖尿病患者组织样本中的 SARS-CoV-2 人类靶点（HT-SARS-CoV-2）ACE2、TMPRSS2 和 FURIN 进行共表达分析。使用 STRING 基于功能蛋白关联分析了 HT-SARS-CoV-2 与免疫系统过程基因之间的网络。此外，还使用 STITCH 确定了可药用靶点。DPP4 是唯一与 ACE2、TMPRSS2 和 FURIN 三个 HT-SARS-CoV-2 基因共表达的免疫系统过程基因，而其他八个免疫基因至少与两个 HT-SARS-CoV-2 基因共表达。在免疫和 HT-SARS-CoV-2 基因之间进行 STRING 分析，绘制了 19 个关联，其中在混合健康（323）和泛癌（11003）组织中存在 8 个共同网络基因，此外还包括正常（87）、癌症（90）和糖尿病（128）胰腺组织。使用这种方法，鉴定出了 HT-SARS-CoV-2 与免疫系统过程基因之间三个普遍适用的可药用连接。这些连接包括 ACE2-DPP4 和 TMPRSS2-SRC 的正关联以及 FURIN 与 ADAM17 的负关联。此外，从 STITCH 中提取了 16 种药物（评分<0.8），其中包含 32 个靶基因。因此，使用生物信息学工具鉴定了与 HT-SARS-CoV-2 相关的免疫网络，为 COVID-19 带来了新的治疗机会。
