Shahjaman Md, Rezanur Rahman Md, Rabiul Auwul Md
Department of Statistics, Begum Rokeya University, Rangpur, 5400, Bangladesh.
Department of Biotechnology and Genetic Engineering, Islamic University, Kushtia, Bangladesh.
Inform Med Unlocked. 2021;25:100702. doi: 10.1016/j.imu.2021.100702. Epub 2021 Aug 18.
The novel coronavirus (SARS-CoV-2) has expanded rapidly worldwide. Now it has covered more than 150 countries worldwide. It is referred to as COVID-19. SARS-CoV-2 mainly affects the respiratory systems of humans that can lead up to serious illness or even death in the presence of different comorbidities. However, most COVID-19 infected people show mild to moderate symptoms, and no medication is suggested. Still, drugs of other diseases have been used to treat COVID-19. Nevertheless, the absence of vaccines and proper drugs against the COVID-19 virus has increased the mortality rate. Albeit sex is a risk factor for COVID-19, none of the studies considered this risk factor for identifying biomarkers from the RNASeq count dataset. Men are more likely to undertake severe symptoms with different comorbidities and show greater mortality compared with women. From this standpoint, we aim to identify shared gene signatures between males and females from the human COVID-19 RNAseq count dataset of peripheral blood cells using a robust voom approach. We identified 1341 overlapping DEGs between male and female datasets. The gene ontology (GO) annotation and pathway enrichment analysis revealed that DEGs are involved in various BP categories such as nucleosome assembly, DNA conformation change, DNA packaging, and different KEGG pathways such as cell cycle, ECM-receptor interaction, progesterone-mediated oocyte maturation, etc. Ten hub-proteins (UBC, KIAA0101, APP, CDK1, SUMO2, SP1, FN1, CDK2, E2F1, and TP53) were unveiled using PPI network analysis. The top three miRNAs (mir-17-5p, mir-20a-5p, mir-93-5p) and TFs (PPARG, E2F1 and KLF5) were uncovered. In conclusion, the top ten significant drugs (roscovitine, curcumin, simvastatin, fulvestrant, troglitazone, alvocidib, L-alanine, tamoxifen, serine, and doxorubicin) were retrieved using drug repurposing analysis of overlapping DEGs, which might be therapeutic agents of COVID-19.
新型冠状病毒(SARS-CoV-2)已在全球迅速传播。目前,它已覆盖全球150多个国家。它被称为COVID-19。SARS-CoV-2主要影响人类的呼吸系统,在存在不同合并症的情况下,可能导致严重疾病甚至死亡。然而,大多数COVID-19感染者表现出轻至中度症状,不建议用药。尽管如此,其他疾病的药物已被用于治疗COVID-19。尽管如此,缺乏针对COVID-19病毒的疫苗和合适药物增加了死亡率。尽管性别是COVID-19的一个风险因素,但没有一项研究在从RNA序列计数数据集中识别生物标志物时考虑这个风险因素。与女性相比,男性更有可能出现伴有不同合并症的严重症状,且死亡率更高。从这个角度出发,我们旨在使用一种强大的voom方法,从人类COVID-19外周血细胞RNA序列计数数据集中识别男性和女性之间共享的基因特征。我们在男性和女性数据集之间鉴定出1341个重叠的差异表达基因(DEG)。基因本体(GO)注释和通路富集分析表明,DEG参与了各种生物学过程(BP)类别,如核小体组装、DNA构象变化、DNA包装,以及不同的京都基因与基因组百科全书(KEGG)通路,如细胞周期、细胞外基质-受体相互作用、孕酮介导的卵母细胞成熟等。使用蛋白质-蛋白质相互作用(PPI)网络分析揭示了十个枢纽蛋白(泛素结合酶E2、KIAA0101、淀粉样前体蛋白、周期蛋白依赖性激酶1、小泛素样修饰蛋白2、特异性蛋白1、纤连蛋白1、周期蛋白依赖性激酶2、E2F转录因子1和肿瘤蛋白p53)。发现了前三个微小RNA(mir-17-5p、mir-20a-5p、mir-93-5p)和转录因子(过氧化物酶体增殖物激活受体γ、E2F1和Krüppel样因子5)。总之,通过对重叠DEG进行药物再利用分析,检索到了十种重要药物(roscovitine、姜黄素、辛伐他汀、氟维司群、曲格列酮、阿沃西地布、L-丙氨酸、他莫昔芬、丝氨酸和阿霉素),它们可能是COVID-19的治疗药物。