Institute for System Analysis and Computer Science "Antonio Ruberti", National Research Council of Italy, 00185 Rome, Italy.
Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, 02-097 Warsaw, Poland.
Viruses. 2023 May 18;15(5):1188. doi: 10.3390/v15051188.
SARS-CoV-2 and its many variants have caused a worldwide emergency. Host cells colonised by SARS-CoV-2 present a significantly different gene expression landscape. As expected, this is particularly true for genes that directly interact with virus proteins. Thus, understanding the role that transcription factors can play in driving differential regulation in patients affected by COVID-19 is a focal point to unveil virus infection. In this regard, we have identified 19 transcription factors which are predicted to target human proteins interacting with Spike glycoprotein of SARS-CoV-2. Transcriptomics RNA-Seq data derived from 13 human organs are used to analyse expression correlation between identified transcription factors and related target genes in both COVID-19 patients and healthy individuals. This resulted in the identification of transcription factors showing the most relevant impact in terms of most evident differential correlation between COVID-19 patients and healthy individuals. This analysis has also identified five organs such as the blood, heart, lung, nasopharynx and respiratory tract in which a major effect of differential regulation mediated by transcription factors is observed. These organs are also known to be affected by COVID-19, thereby providing consistency to our analysis. Furthermore, 31 key human genes differentially regulated by the transcription factors in the five organs are identified and the corresponding KEGG pathways and GO enrichment are also reported. Finally, the drugs targeting those 31 genes are also put forth. This in silico study explores the effects of transcription factors on human genes interacting with Spike glycoprotein of SARS-CoV-2 and intends to provide new insights to inhibit the virus infection.
SARS-CoV-2 及其众多变体引发了全球紧急情况。被 SARS-CoV-2 殖民的宿主细胞呈现出明显不同的基因表达谱。正如预期的那样，这在与病毒蛋白直接相互作用的基因中尤其如此。因此，了解转录因子在驱动 COVID-19 患者中差异调节方面可以发挥的作用，是揭示病毒感染的一个重点。在这方面，我们已经确定了 19 个转录因子，这些转录因子被预测可以靶向与 SARS-CoV-2 的刺突糖蛋白相互作用的人类蛋白。使用来自 13 个人类器官的转录组学 RNA-Seq 数据，分析 COVID-19 患者和健康个体中鉴定出的转录因子与相关靶基因之间的表达相关性。这导致确定了转录因子，这些转录因子在 COVID-19 患者和健康个体之间的差异相关性方面表现出最相关的影响。该分析还确定了五个器官，如血液、心脏、肺、鼻咽和呼吸道，在这些器官中观察到转录因子介导的差异调节的主要影响。这些器官也已知受到 COVID-19 的影响，从而为我们的分析提供了一致性。此外，还鉴定了 31 个在这五个器官中由转录因子差异调节的关键人类基因，并且还报告了相应的 KEGG 途径和 GO 富集。最后，还提出了针对这些 31 个基因的药物。这项计算机研究探讨了转录因子对与 SARS-CoV-2 的刺突糖蛋白相互作用的人类基因的影响，并旨在为抑制病毒感染提供新的见解。
