Khorsand Babak, Savadi Abdorreza, Naghibzadeh Mahmoud
Department of Computer Engineering, Faculty of Engineering, Ferdowsi University of Mashhad, Mashhad, Iran.
Inform Med Unlocked. 2020;20:100413. doi: 10.1016/j.imu.2020.100413. Epub 2020 Aug 13.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus which caused the coronavirus disease 2019 pandemic and infected more than 12 million victims and resulted in over 560,000 deaths in 213 countries around the world. Having no symptoms in the first week of infection increases the rate of spreading the virus. The increasing rate of the number of infected individuals and its high mortality necessitates an immediate development of proper diagnostic methods and effective treatments. SARS-CoV-2, similar to other viruses, needs to interact with the host proteins to reach the host cells and replicate its genome. Consequently, virus-host protein-protein interaction (PPI) identification could be useful in predicting the behavior of the virus and the design of antiviral drugs. Identification of virus-host PPIs using experimental approaches are very time consuming and expensive. Computational approaches could be acceptable alternatives for many preliminary investigations. In this study, we developed a new method to predict SARS-CoV-2-human PPIs. Our model is a three-layer network in which the first layer contains the most similar Alphainfluenzavirus proteins to SARS-CoV-2 proteins. The second layer contains protein-protein interactions between Alphainfluenzavirus proteins and human proteins. The last layer reveals protein-protein interactions between SARS-CoV-2 proteins and human proteins by using the clustering coefficient network property on the first two layers. To further analyze the results of our prediction network, we investigated human proteins targeted by SARS-CoV-2 proteins and reported the most central human proteins in human PPI network. Moreover, differentially expressed genes of previous researches were investigated and PPIs of SARS-CoV-2-human network, the human proteins of which were related to upregulated genes, were reported.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是引发2019年冠状病毒病大流行的新型冠状病毒,在全球213个国家感染了超过1200万人,导致超过56万人死亡。感染第一周没有症状会增加病毒传播率。受感染个体数量的增加率及其高死亡率使得必须立即开发合适的诊断方法和有效治疗方法。与其他病毒一样,SARS-CoV-2需要与宿主蛋白相互作用才能进入宿主细胞并复制其基因组。因此,病毒-宿主蛋白质-蛋白质相互作用(PPI)的鉴定有助于预测病毒行为和设计抗病毒药物。使用实验方法鉴定病毒-宿主PPI非常耗时且昂贵。计算方法可以作为许多初步研究的可接受替代方案。在本研究中,我们开发了一种预测SARS-CoV-2与人类PPI的新方法。我们的模型是一个三层网络,其中第一层包含与SARS-CoV-2蛋白最相似的甲型流感病毒蛋白。第二层包含甲型流感病毒蛋白与人类蛋白之间的蛋白质-蛋白质相互作用。最后一层通过在前两层上使用聚类系数网络属性揭示SARS-CoV-2蛋白与人类蛋白之间的蛋白质-蛋白质相互作用。为了进一步分析我们预测网络的结果,我们研究了SARS-CoV-2蛋白靶向的人类蛋白,并报告了人类PPI网络中最核心的人类蛋白。此外,我们还研究了先前研究中的差异表达基因,并报告了SARS-CoV-2与人类网络中人类蛋白与上调基因相关的PPI。