Human-nCoV蛋白质相互作用网络的计算建模
Computational modeling of Human-nCoV protein-protein interaction network
摘要：
2019冠状病毒病于二零二零年造成全球大流行，发病率及死亡率高。新型冠状病毒（nCoV），也称为严重急性呼吸道综合征冠状病毒2（SARS-CoV 2），是这种致命疾病的罪魁祸首。国际病毒分类委员会（ICTV）已宣布nCoV与2003年流行的SARS-CoV在基因上高度相似（89%相似性）。文献中可获得有限数量的临床验证的人-nCoV蛋白相互作用数据。基于这一假设，本研究利用实验验证的SARS-CoV-Human蛋白质相互作用网络，建立了nCoV-Human蛋白质相互作用网络的计算模型。首先，在SARS-CoV-人相互作用网络中，使用易感-感染-易感（SIS）模型鉴定水平1和水平2的人传播蛋白。这些蛋白被认为是nCoV诱饵蛋白的潜在人类靶标。基于基因本体的模糊亲和函数已被用于构建nCoV-人蛋白相互作用网络，特异性阈值为99.98%。这也确定了人类蛋白质相互作用网络中COVID-19的1级人类传播者。随后使用SIS模型识别2级人类传播者。最终使用7种潜在的FDA上市的COVID-19药物验证了衍生的宿主-病原体相互作用网络，其中已知药物靶蛋白和鉴定的扩展蛋白之间存在显著重叠。
英文摘要：
COVID-19 has created a global pandemic with high morbidity and mortality in 2020. Novel coronavirus (nCoV), also known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), is responsible for this deadly disease. International Committee on Taxonomy of Viruses (ICTV) has declared that nCoV is highly genetically similar to SARS-CoV epidemic in 2003 (89% similarity). Limited number of clinically validated Human-nCoV protein interaction data is available in the literature. With this hypothesis, the present work focuses on developing a computational model for nCoV-Human protein interaction network, using the experimentally validated SARS-CoV-Human protein interactions. Initially, level-1 and level-2 human spreader proteins are identified in SARS-CoV-Human interaction network, using Susceptible-Infected-Susceptible (SIS) model. These proteins are considered as potential human targets for nCoV bait proteins. A gene-ontology based fuzzy affinity function has been used to construct the nCoV-Human protein interaction network at 99.98% specificity threshold. This also identifies the level-1 human spreaders for COVID-19 in human protein-interaction network. Level-2 human spreaders are subsequently identified using the SIS model. The derived host-pathogen interaction network is finally validated using 7 potential FDA listed drugs for COVID-19 with significant overlap between the known drug target proteins and the identified spreader proteins.
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