Islam M Babul, Chowdhury Utpala Nanda, Nashiry Md Asif, Moni Mohammad Ali
Department of Electrical and Electronic Engineering, University of Rajshahi, Rajshahi, Bangladesh.
Department of Computer Science and Engineering, University of Rajshahi, Rajshahi, Bangladesh.
Inform Med Unlocked. 2022;34:101116. doi: 10.1016/j.imu.2022.101116. Epub 2022 Oct 28.
Coronavirus disease 2019 (COVID-19)-driven global pandemic triggered innumerable health complications, imposing great challenges in managing other respiratory diseases like asthma. Furthermore, increases in the underlying inflammation involved in the fatality of COVID-19 have been linked with lack of vitamin D. In this research work, we intend to investigate the possible genetic linkage of asthma and vitamin D deficiency with the severity and fatality of COVID-19 using a network-based approach. We identified and analysed 41 and 14 differentially expressed genes (DEGs) of COVID-19 being common with asthma and vitamin D deficiency, respectively, through the comparative differential gene expression analysis and their footprints on signalling pathways. Gene set enrichment analysis for GO terms and signalling pathways reveals key biological activities, including inflammatory response-related pathways (e.g., cytokine- and chemokine-mediated signalling pathways, IL-17, and TNF signalling pathways). Besides, the Protein-Protein Interaction network analysis of those DEGs reveals hub proteins, some of which are reported as inflammatory antiviral interferon-stimulated biomarkers that potentially drive the cytokine storm leading to COVID-19 severity and fatality, and contributes in the early stage of viral replication, respectively. Moreover, the regulatory network analysis found these DEGs associated with antiviral and tumour inhibitory transcription factors and micro-RNAs. Finally, drug-target enrichment analysis yields , , , and , which have been reported to be effective in suppressing the pro-inflammatory cytokines production, and other respiratory tract infections. Our results yield shared biomarker-driven key hypotheses followed by network-based analytics, demystifying the mechanistic details of COVID-19 comorbidity of asthma and vitamin D deficiency with their potential therapeutic implications.
2019年冠状病毒病（COVID-19）引发的全球大流行引发了无数健康并发症，给哮喘等其他呼吸道疾病的管理带来了巨大挑战。此外，COVID-19致死率所涉及的潜在炎症增加与维生素D缺乏有关。在这项研究工作中，我们打算使用基于网络的方法研究哮喘和维生素D缺乏与COVID-19严重程度和致死率之间可能的遗传联系。通过比较差异基因表达分析及其在信号通路中的印记，我们分别鉴定并分析了41个和14个与哮喘和维生素D缺乏共同存在的COVID-19差异表达基因（DEG）。对基因本体（GO）术语和信号通路的基因集富集分析揭示了关键的生物学活性，包括炎症反应相关通路（例如，细胞因子和趋化因子介导的信号通路、IL-17和TNF信号通路）。此外，对这些DEG的蛋白质-蛋白质相互作用网络分析揭示了枢纽蛋白，其中一些被报道为炎症抗病毒干扰素刺激的生物标志物，它们可能分别驱动导致COVID-19严重程度和致死率的细胞因子风暴，并在病毒复制的早期阶段发挥作用。此外，调控网络分析发现这些DEG与抗病毒和肿瘤抑制转录因子以及微小RNA相关。最后，药物靶点富集分析产生了[具体药物名称1]、[具体药物名称2]、[具体药物名称3]和[具体药物名称4]，据报道这些药物在抑制促炎细胞因子产生以及其他呼吸道感染方面有效。我们的结果产生了由共享生物标志物驱动的关键假设，随后进行基于网络的分析，揭开了哮喘和维生素D缺乏与COVID-19合并症的机制细节及其潜在治疗意义。
