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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
Network analysis of host-pathogen protein interactions in microbe induced cardiovascular diseases
Nirupma Singh1, Sneha Rai1, Rakesh Bhatnagar2
1Computational and Structural Biology Laboratory, Department of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi, India.
Insights
Investigating host-pathogen interactions (HPIs) in microbe-induced cardiovascular diseases (CVDs) reveals key proteins and pathways driving pathogenicity. This analysis identifies specific HPIs and host mimicry domains crucial for understanding cardiac damage.
Area of Science:
- Microbiology and Bioinformatics
- Cardiovascular Research
- Systems Biology
Background:
- Understanding host-pathogen interactions (HPIs) is vital for elucidating the mechanisms of microbial pathogenesis in cardiovascular diseases (CVDs).
- Comparing HPIs in CVD-associated pathogens with all known HPIs can pinpoint pathways specific to CVD development.
Purpose of the Study:
- To analyze the topological properties of HPI networks in CVDs and across all pathogens.
- To identify specific HPIs, proteins, and pathways involved in microbe-induced CVDs.
Main Methods:
- Network analysis of HPIs using Cytoscape 3.5.1.
- Ontology and pathway enrichment analysis with KOBAS 3.0.
- Identification of central and essential proteins and host mimicry domains.
Main Results:
- Papilloma, Herpes, Influenza A virus, Yersinia pestis, and Bacillus anthracis HPIs were prominent in both whole and CVD-specific networks.
- Central viral and bacterial secretory proteins were identified as virulent, with viral proteins showing more host interactions.
- Key host proteins (e.g., Alpha-synuclein) and pathways (e.g., ubiquitin-mediated proteolysis) specific to CVDs were identified.
- Enriched host mimicry domains (DEXDc, HELICc) suggest pathogen strategies for hijacking cellular machinery.
Conclusions:
- This study provides a systems-level understanding of cardiac damage mechanisms in microbe-induced CVDs.
- Identified HPIs, proteins, and pathways offer potential targets for therapeutic interventions.
Abstract:
Large-scale visualization and analysis of HPIs involved in microbial CVDs can provide crucial insights into the mechanisms of pathogenicity. The comparison of CVD associated HPIs with the entire set of HPIs can identify the pathways specific to CVDs. Therefore, topological properties of HPI networks in CVDs and all pathogens was studied using Cytoscape3.5.1. Ontology and pathway analysis were done using KOBAS 3.0. HPIs of Papilloma, Herpes, Influenza A virus as well as Yersinia pestis and Bacillus anthracis among bacteria were predominant in the whole (wHPI) and the CVD specific (cHPI) network. The central viral and secretory bacterial proteins were predicted virulent. The central viral proteins had higher number of interactions with host proteins in comparison with bacteria. Major fraction of central and essential host proteins interacts with central viral proteins. Alpha-synuclein, Ubiquitin ribosomal proteins, TATA-box-binding protein, and Polyubiquitin-C &B proteins were the top interacting proteins specific to CVDs. Signaling by NGF, Fc epsilon receptor, EGFR and ubiquitin mediated proteolysis were among the top enriched CVD specific pathways. DEXDc and HELICc were enriched host mimicry domains that may help in hijacking of cellular machinery by pathogens. This study provides a system level understanding of cardiac damage in microbe induced CVDs.
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