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基因互作网络解析肠道细菌在心血管疾病中的作用:大肠杆菌 O157:H7 宿主-细菌相互作用研究。

Gene interaction network to unravel the role of gut bacterial species in cardiovascular diseases: E. coli O157:H7 host-bacterial interaction study.

机构信息

Medical and Biological Computing Laboratory, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, 632014, Tamil Nadu, India.

Medical and Biological Computing Laboratory, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, 632014, Tamil Nadu, India.

出版信息

Comput Biol Med. 2021 Jun;133:104417. doi: 10.1016/j.compbiomed.2021.104417. Epub 2021 Apr 21.

Abstract

BACKGROUND

Cardiovascular Disease (CVD) is one of the most common causes of mortality in humans. Presently, the role of pathogens in the initiation and progression of the CVDs is not clearly understood. Hence, it is essential to understand the molecular-level interactions between the human proteins and the microbial proteins to deduce their functional roles in the CVDs.

METHOD

The host-pathogen interactions (HPI) related to CVDs in the case of E. coli str. O157:H7 colonization were curated, and also the protein-protein interactions (PPI) between humans and E. coli were collected. Gene interaction network (GIN) and functional enrichment analyses (FEA) were utilized for this.

RESULTS

The GIN revealed dense interactions between the functional partners. The FEA indicated that the essential pathways played a significant role in humans as well as in E. coli. The primary responses against most of the bacterial pathogens in humans are different from that of E. coli; Terpenoid biosynthesis and production of secondary metabolite pathways aid the survival of the E. coli inside the host. Interestingly, network analysis divulged that the E. coli genes ksgA, rpsT, ispE, rpsI, ispH, and the human genes TP53, CASP3, CYCS, EP300, RHOA communicated by significant numbers in direct interactions.

CONCLUSIONS

The results obtained from the present study will help researchers understand the molecular-level interactions in the CVDs between the human and the E. coli genes. The important genes with vital interactions can be considered as hub molecules and can be exploited for new drug discovery.

摘要

背景

心血管疾病(CVD)是人类最常见的死亡原因之一。目前,病原体在 CVD 的发生和发展中的作用尚不清楚。因此,了解人类蛋白与微生物蛋白之间的分子水平相互作用对于推断它们在 CVD 中的功能作用至关重要。

方法

对大肠杆菌 O157:H7 定植引起的 CVD 的宿主-病原体相互作用(HPI)进行了整理,并收集了人类与大肠杆菌之间的蛋白-蛋白相互作用(PPI)。利用基因相互作用网络(GIN)和功能富集分析(FEA)进行了分析。

结果

GIN 揭示了功能伙伴之间的密集相互作用。FEA 表明,关键途径在人类和大肠杆菌中都发挥了重要作用。人类对大多数细菌病原体的主要反应与大肠杆菌不同;萜类生物合成和次生代谢产物途径的产生有助于大肠杆菌在宿主内的存活。有趣的是,网络分析揭示,大肠杆菌基因 ksgA、rpsT、ispE、rpsI、ispH 和人类基因 TP53、CASP3、CYCS、EP300、RHOA 通过直接相互作用进行了大量通讯。

结论

本研究获得的结果将帮助研究人员了解人类和大肠杆菌基因之间 CVD 的分子水平相互作用。具有重要相互作用的重要基因可以被视为枢纽分子,并可用于新药发现。

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