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基于系统生物学的方法构建流感 A 病毒与其宿主的全蛋白相互作用网络。

A systems biology-driven approach to construct a comprehensive protein interaction network of influenza A virus with its host.

机构信息

Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing, 100124, China.

Faculty of Information Technology, Beijing University of Technology, Beijing, 100124, China.

出版信息

BMC Infect Dis. 2020 Jul 6;20(1):480. doi: 10.1186/s12879-020-05214-0.

Abstract

BACKGROUND

Influenza A virus (IAV) infection is a serious public health problem not only in South East Asia but also in European and African countries. Scientists are using network biology to dig deep into the essential host factors responsible for regulation of virus infections. Researchers can explore the virus invasion into the host cells by studying the virus-host relationship based on their protein-protein interaction network.

METHODS

In this study, we present a comprehensive IAV-host protein-protein interaction network that is obtained based on the literature-curated protein interaction datasets and some important interaction databases. The network is constructed in Cytoscape and analyzed with its plugins including CytoHubba, CytoCluster, MCODE, ClusterViz and ClusterOne. In addition, Gene Ontology and KEGG enrichment analyses are performed on the highly IAV-associated human proteins. We also compare the current results with those from our previous study on Hepatitis C Virus (HCV)-host protein-protein interaction network in order to find out valuable information.

RESULTS

We found out 1027 interactions among 829 proteins of which 14 are viral proteins and 815 belong to human proteins. The viral protein NS1 has the highest number of associations with human proteins followed by NP, PB2 and so on. Among human proteins, LNX2, MEOX2, TFCP2, PRKRA and DVL2 have the most interactions with viral proteins. Based on KEGG pathway enrichment analysis of the highly IAV-associated human proteins, we found out that they are enriched in the KEGG pathway of basal cell carcinoma. Similarly, the result of KEGG analysis of the common host factors involved in IAV and HCV infections shows that these factors are enriched in the infection pathways of Hepatitis B Virus (HBV), Viral Carcinoma, measles and certain other viruses.

CONCLUSION

It is concluded that the list of proteins we identified might be used as potential drug targets for the drug design against the infectious diseases caused by Influenza A Virus and other viruses.

摘要

背景

甲型流感病毒(IAV)感染不仅是东南亚地区,也是欧洲和非洲国家的严重公共卫生问题。科学家们正在利用网络生物学深入挖掘负责调节病毒感染的基本宿主因素。通过研究基于病毒-宿主相互作用网络的病毒入侵宿主细胞,研究人员可以探索病毒与宿主的关系。

方法

在这项研究中,我们展示了一个综合的 IAV-宿主蛋白质-蛋白质相互作用网络,该网络是基于文献整理的蛋白质相互作用数据集和一些重要的相互作用数据库获得的。该网络是在 Cytoscape 中构建的,并使用其插件(包括 CytoHubba、CytoCluster、MCODE、ClusterViz 和 ClusterOne)进行分析。此外,对与 IAV 高度相关的人类蛋白质进行了基因本体论和 KEGG 富集分析。我们还将当前的结果与我们之前关于丙型肝炎病毒(HCV)-宿主蛋白质-蛋白质相互作用网络的研究结果进行了比较,以找出有价值的信息。

结果

我们发现了 829 个蛋白质之间的 1027 个相互作用,其中 14 个是病毒蛋白,815 个属于人类蛋白。病毒蛋白 NS1 与人类蛋白的关联数量最多,其次是 NP、PB2 等。在人类蛋白中,与病毒蛋白关联最多的是 LNX2、MEOX2、TFCP2、PRKRA 和 DVL2。基于与 IAV 高度相关的人类蛋白的 KEGG 途径富集分析,我们发现它们富集在基底细胞癌的 KEGG 途径中。同样,涉及 IAV 和 HCV 感染的共同宿主因子的 KEGG 分析结果表明,这些因子富集在乙型肝炎病毒(HBV)、病毒性癌、麻疹和某些其他病毒的感染途径中。

结论

我们确定的蛋白质列表可能被用作针对甲型流感病毒和其他病毒引起的传染病的药物设计的潜在药物靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6706/7339526/92a49b124fed/12879_2020_5214_Fig1_HTML.jpg

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