严重急性呼吸系统综合征冠状病毒2型调节宿主蛋白与计算预测PPIs的相互作用:来自翻译系统生物学研究的见解

Kalyani B. Karunakaran, N. Balakrishnan, M. Ganapathiraju
{"title":"严重急性呼吸系统综合征冠状病毒2型调节宿主蛋白与计算预测PPIs的相互作用:来自翻译系统生物学研究的见解","authors":"Kalyani B. Karunakaran, N. Balakrishnan, M. Ganapathiraju","doi":"10.3389/fsysb.2022.815237","DOIUrl":null,"url":null,"abstract":"Accelerated efforts to identify intervention strategies for the COVID-19 pandemic caused by SARS-CoV-2 need to be supported by deeper investigations into host invasion and response mechanisms. We constructed the neighborhood interactome network of the 332 human proteins targeted by SARS-CoV-2 proteins, augmenting it with 1,941 novel human protein-protein interactions predicted using our High-precision Protein-Protein Interaction Prediction (HiPPIP) model. Novel interactors, and the interactome as a whole, showed significant enrichment for genes differentially expressed in SARS-CoV-2-infected A549 and Calu-3 cells, postmortem lung samples of COVID-19 patients and blood samples of COVID-19 patients with severe clinical outcomes. The PPIs connected host proteins to COVID-19 blood biomarkers, ACE2 (SARS-CoV-2 entry receptor), genes differentiating SARS-CoV-2 infection from other respiratory virus infections, and SARS-CoV-targeted host proteins. Novel PPIs facilitated identification of the cilium organization functional module; we deduced the potential antiviral role of an interaction between the virus-targeted NUP98 and the cilia-associated CHMP5. Functional enrichment analyses revealed promyelocytic leukaemia bodies, midbody, cell cycle checkpoints and tristetraprolin pathway as potential viral targets. Network proximity of diabetes and hypertension associated genes to host proteins indicated a mechanistic basis for these co-morbidities in critically ill/non-surviving patients. Twenty-four drugs were identified using comparative transcriptome analysis, which include those undergoing COVID-19 clinical trials, showing broad-spectrum antiviral properties or proven activity against SARS-CoV-2 or SARS-CoV/MERS-CoV in cell-based assays. The interactome is available on a webserver at http://severus.dbmi.pitt.edu/corona/.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":"{\"title\":\"Interactome of SARS-CoV-2 Modulated Host Proteins With Computationally Predicted PPIs: Insights From Translational Systems Biology Studies\",\"authors\":\"Kalyani B. Karunakaran, N. Balakrishnan, M. Ganapathiraju\",\"doi\":\"10.3389/fsysb.2022.815237\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Accelerated efforts to identify intervention strategies for the COVID-19 pandemic caused by SARS-CoV-2 need to be supported by deeper investigations into host invasion and response mechanisms. We constructed the neighborhood interactome network of the 332 human proteins targeted by SARS-CoV-2 proteins, augmenting it with 1,941 novel human protein-protein interactions predicted using our High-precision Protein-Protein Interaction Prediction (HiPPIP) model. Novel interactors, and the interactome as a whole, showed significant enrichment for genes differentially expressed in SARS-CoV-2-infected A549 and Calu-3 cells, postmortem lung samples of COVID-19 patients and blood samples of COVID-19 patients with severe clinical outcomes. The PPIs connected host proteins to COVID-19 blood biomarkers, ACE2 (SARS-CoV-2 entry receptor), genes differentiating SARS-CoV-2 infection from other respiratory virus infections, and SARS-CoV-targeted host proteins. Novel PPIs facilitated identification of the cilium organization functional module; we deduced the potential antiviral role of an interaction between the virus-targeted NUP98 and the cilia-associated CHMP5. Functional enrichment analyses revealed promyelocytic leukaemia bodies, midbody, cell cycle checkpoints and tristetraprolin pathway as potential viral targets. Network proximity of diabetes and hypertension associated genes to host proteins indicated a mechanistic basis for these co-morbidities in critically ill/non-surviving patients. Twenty-four drugs were identified using comparative transcriptome analysis, which include those undergoing COVID-19 clinical trials, showing broad-spectrum antiviral properties or proven activity against SARS-CoV-2 or SARS-CoV/MERS-CoV in cell-based assays. The interactome is available on a webserver at http://severus.dbmi.pitt.edu/corona/.\",\"PeriodicalId\":73109,\"journal\":{\"name\":\"Frontiers in systems biology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-04-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in systems biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3389/fsysb.2022.815237\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in systems biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/fsysb.2022.815237","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 3

摘要

需要通过对宿主入侵和反应机制进行更深入的调查来支持加快确定由SARS-CoV-2引起的新冠肺炎大流行的干预策略。我们构建了由332种严重急性呼吸系统综合征冠状病毒2型蛋白靶向的人类蛋白质组成的邻域相互作用组网络,并使用我们的高精度蛋白质-蛋白质相互作用预测(HiPPIP)模型预测了1941种新的人类蛋白质-蛋白质的相互作用。新的相互作用体和整个相互作用体显示,在受SARS-CoV-2感染的A549和Calu-3细胞、新冠肺炎患者的死后肺样本和具有严重临床结果的新冠肺炎患者的血液样本中,差异表达的基因显著富集。PPI将宿主蛋白与新冠肺炎血液生物标志物、ACE2(SARS-CoV-2进入受体)、区分SARS-CoV-2感染与其他呼吸道病毒感染的基因以及SARS-CoV靶向宿主蛋白连接。新型PPI促进纤毛组织功能模块的识别;我们推断了病毒靶向的NUP98和纤毛相关的CHMP5之间的相互作用的潜在抗病毒作用。功能富集分析显示,早幼粒细胞白血病小体、中体细胞、细胞周期检查点和三四脯氨酸途径是潜在的病毒靶点。糖尿病和高血压相关基因与宿主蛋白的网络接近性表明了危重症/非存活患者中这些合并症的机制基础。使用比较转录组分析鉴定了20种药物,其中包括正在接受新冠肺炎临床试验的药物,这些药物在基于细胞的测定中显示出广谱抗病毒特性或已证明对SARS-CoV-2或SARS-CoV/MERS-CoV具有活性。该互动工具可在以下网址的网络服务器上获得:http://severus.dbmi.pitt.edu/corona/.
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Interactome of SARS-CoV-2 Modulated Host Proteins With Computationally Predicted PPIs: Insights From Translational Systems Biology Studies
Accelerated efforts to identify intervention strategies for the COVID-19 pandemic caused by SARS-CoV-2 need to be supported by deeper investigations into host invasion and response mechanisms. We constructed the neighborhood interactome network of the 332 human proteins targeted by SARS-CoV-2 proteins, augmenting it with 1,941 novel human protein-protein interactions predicted using our High-precision Protein-Protein Interaction Prediction (HiPPIP) model. Novel interactors, and the interactome as a whole, showed significant enrichment for genes differentially expressed in SARS-CoV-2-infected A549 and Calu-3 cells, postmortem lung samples of COVID-19 patients and blood samples of COVID-19 patients with severe clinical outcomes. The PPIs connected host proteins to COVID-19 blood biomarkers, ACE2 (SARS-CoV-2 entry receptor), genes differentiating SARS-CoV-2 infection from other respiratory virus infections, and SARS-CoV-targeted host proteins. Novel PPIs facilitated identification of the cilium organization functional module; we deduced the potential antiviral role of an interaction between the virus-targeted NUP98 and the cilia-associated CHMP5. Functional enrichment analyses revealed promyelocytic leukaemia bodies, midbody, cell cycle checkpoints and tristetraprolin pathway as potential viral targets. Network proximity of diabetes and hypertension associated genes to host proteins indicated a mechanistic basis for these co-morbidities in critically ill/non-surviving patients. Twenty-four drugs were identified using comparative transcriptome analysis, which include those undergoing COVID-19 clinical trials, showing broad-spectrum antiviral properties or proven activity against SARS-CoV-2 or SARS-CoV/MERS-CoV in cell-based assays. The interactome is available on a webserver at http://severus.dbmi.pitt.edu/corona/.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Transporter annotations are holding up progress in metabolic modeling Life’s building blocks: the modular path to multiscale complexity Coupling quantitative systems pharmacology modelling to machine learning and artificial intelligence for drug development: its pAIns and gAIns Predicting chronic responses to calcium channel blockade with a virtual population of African Americans with hypertensive chronic kidney disease Building an Adverse Outcome Pathway network for COVID-19
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1