scholarly journals Comprehensive host-pathogen protein-protein interaction network analysis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Babak Khorsand ◽  
Abdorreza Savadi ◽  
Mahmoud Naghibzadeh
Keyword(s):  
Protein Interaction ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Essential Proteins ◽  
Protein Protein Interaction ◽  
Host Pathogen ◽  
Pathogen Protein ◽  
Human Proteins ◽  
Protein Protein Interaction Network ◽  
Virus Proteins

Abstract Background Infectious diseases are a cruel assassin with millions of victims around the world each year. Understanding infectious mechanism of viruses is indispensable for their inhibition. One of the best ways of unveiling this mechanism is to investigate the host-pathogen protein-protein interaction network. In this paper we try to disclose many properties of this network. We focus on human as host and integrate experimentally 32,859 interaction between human proteins and virus proteins from several databases. We investigate different properties of human proteins targeted by virus proteins and find that most of them have a considerable high centrality scores in human intra protein-protein interaction network. Investigating human proteins network properties which are targeted by different virus proteins can help us to design multipurpose drugs. Results As host-pathogen protein-protein interaction network is a bipartite network and centrality measures for this type of networks are scarce, we proposed seven new centrality measures for analyzing bipartite networks. Applying them to different virus strains reveals unrandomness of attack strategies of virus proteins which could help us in drug design hence elevating the quality of life. They could also be used in detecting host essential proteins. Essential proteins are those whose functions are critical for survival of its host. One of the proposed centralities named diversity of predators, outperforms the other existing centralities in terms of detecting essential proteins and could be used as an optimal essential proteins’ marker. Conclusions Different centralities were applied to analyze human protein-protein interaction network and to detect characteristics of human proteins targeted by virus proteins. Moreover, seven new centralities were proposed to analyze host-pathogen protein-protein interaction network and to detect pathogens’ favorite host protein victims. Comparing different centralities in detecting essential proteins reveals that diversity of predator (one of the proposed centralities) is the best essential protein marker.

scholarly journals Insight into Bacterial Virulence Mechanisms against Host Immune Response via the Yersinia pestis-Human Protein-Protein Interaction Network

2011 ◽  
Vol 79 (11) ◽  
pp. 4413-4424 ◽  
Author(s):  
Huiying Yang ◽  
Yuehua Ke ◽  
Jian Wang ◽  
Yafang Tan ◽  
Sebenzile K. Myeni ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Mapk Signaling ◽  
Human Protein ◽  
Content Type ◽  
Protein Protein Interaction ◽  
Human Proteins ◽  
Protein Protein Interaction Network

ABSTRACTAYersinia pestis-human protein interaction network is reported here to improve our understanding of its pathogenesis. Up to 204 interactions between 66Y. pestisbait proteins and 109 human proteins were identified by yeast two-hybrid assay and then combined with 23 previously published interactions to construct a protein-protein interaction network. Topological analysis of the interaction network revealed that human proteins targeted byY. pestiswere significantly enriched in the proteins that are central in the human protein-protein interaction network. Analysis of this network showed that signaling pathways important for host immune responses were preferentially targeted byY. pestis, including the pathways involved in focal adhesion, regulation of cytoskeleton, leukocyte transendoepithelial migration, and Toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling. Cellular pathways targeted byY. pestisare highly relevant to its pathogenesis. Interactions with host proteins involved in focal adhesion and cytoskeketon regulation pathways could account for resistance ofY. pestisto phagocytosis. Interference with TLR and MAPK signaling pathways byY. pestisreflects common characteristics of pathogen-host interaction that bacterial pathogens have evolved to evade host innate immune response by interacting with proteins in those signaling pathways. Interestingly, a large portion of human proteins interacting withY. pestis(16/109) also interacted with viral proteins (Epstein-Barr virus [EBV] and hepatitis C virus [HCV]), suggesting that viral and bacterial pathogens attack common cellular functions to facilitate infections. In addition, we identified vasodilator-stimulated phosphoprotein (VASP) as a novel interaction partner of YpkA and showed that YpkA could inhibitin vitroactin assembly mediated by VASP.

scholarly journals Network controllability enrichment analysis reveals that SARS-CoV-2 infection tends to target indispensable nodes of a directed human protein-protein interaction network

2021 ◽  
Author(s):  
Ho-Joon Lee
Keyword(s):  
Protein Interaction ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Protein Protein Interaction ◽  
Genome Wide ◽  
A Genome ◽  
Human Proteins ◽  
Protein Protein Interaction Network ◽  
Network Controllability

The COVID-19 disease has been a global threat caused by the new coronavirus species, SARS-CoV-2, since early 2020 with an urgent need for therapeutic interventions. In order to provide insight into human proteins targeted by SARS-CoV-2, here we study a directed human protein-protein interaction network (dhPPIN) based on our previous work on network controllability of virus targets. We previously showed that human proteins targeted by viruses tend to be those whose removal in a dhPPIN requires more control of the network dynamics, which were classified as indispensable nodes. In this study we introduce a more comprehensive rank-based enrichment analysis of our previous dhPPIN for SARS-CoV-2 infection and show that SARS-CoV-2 also tends to target indispensable nodes in the dhPPIN using multiple proteomics datasets, supporting validity and generality of controllability analysis of viral infection in humans. Also, we find differential controllability among SARS-CoV-2, SARS-CoV-1, and MERS-CoV from a comparative proteomics study. Moreover, we show functional significance of indispensable nodes by analyzing heterogeneous datasets from a genome-wide CRISPR screening study, a time-course phosphoproteomics study, and a genome-wide association study. Specifically, we identify SARS-CoV-2 ORF3A as most frequently interacting with indispensable proteins in the dhPPIN, which are enriched in TGF-beta signaling and tend to be sources nodes and interact with each other. Finally, we built an integrated network model of ORF3A-interacting indispensable proteins with multiple functional supports to provide hypotheses for experimental validation as well as therapeutic opportunities. Therefore, a sub-network of indispensable proteins targeted by SARS-CoV-2 could serve as a prioritized network of drug targets and a basis for further functional and mechanistic studies from a network controllability perspective.

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