Prediction of Leishmania Major Key Proteins via Topological Analysis of Protein-Protein Interaction Network

Nasrin Amiri Dashatan,Hakimeh Zali,Mostafa Rezaie Tavirani,Nayebali Ahmadi,Mehdi Koushki

doi:10.31661/gmj.v7i0.1129

Abstract

Background: Although leishmaniasis is regarded as a public health problem, no effective vaccine or decisive treatment has been introduced for this disease. Therefore, representing novel therapeutic proteins is essential. Protein-protein Interaction network analysis is a suitable tool to discover novel drug targets for leishmania major. To this aim, gene and protein expression data is used for instructing protein network and the key proteins are highlighted.Materials and Methods: In this computational and bioinformatics study, the protein/gene expression data related to leishmania major were studied, and 252 candidate proteins were extracted. Then, the protein networks of these proteins were explored and visualized by using String database and Cytoscape software. Finally, clustering and gene ontology were performed by MCODE and PANTHER databases, respectively.Results: Based on gene ontology analysis, most of the leishmania major proteins were located in cell compartments and membrane. Catalytic activity and binding were regarded as the relevant molecular functions and metabolic and cellular processes were the significant biological process. In this network analysis, UB-EP52, EF-2, chaperonin, Hsp70.4, Hsp60, tubulin alpha and beta chain, and ENOL and LACK were introduced as hub-bottleneck proteins. Based on clustering analysis, Lmjf.32.3270, ENOL and Lmjf.13.0290 were determined as seed proteins in each cluster.Conclusion: The results indicated that hub proteins play a significant role in pathogenesis and life cycle of leishmania major. Further studies of hubs will provide a better understanding of leishmaniasis mechanisms. Finally, these key hub proteins could be a suitable and helpful potential for drug targets and treating leishmaniasis by considering their validation. [GMJ.2018;7:e1129]

Highlights

Leishmania, as a protozoan parasite, is considered as the etiological agent of leishmaniasis, which is responsible for a spectrum of disease including cutaneous lesions, disfiguring mucocutaneous, and fetal visceral infection among 98 tropical and subtropical countries such as Iran
Analyzing the topological parameters related to protein-protein interaction (PPI) networks such as degree and betweenness centrality is useful in recognizing the essential proteins in networks and these important proteins can be regarded as the potential drug targets
The present study aims to analyze some topological properties including degree and betweenness centrality related to protein- protein interaction networks of L. major in order to identify hub-bottleneck proteins which can be recommended for new potential drug targets in this parasite

Summary

Introduction

Leishmania, as a protozoan parasite, is considered as the etiological agent of leishmaniasis, which is responsible for a spectrum of disease including cutaneous lesions, disfiguring mucocutaneous, and fetal visceral infection among 98 tropical and subtropical countries such as Iran. Identifying and developing several new key/significant proteins as potential drug targets play a pivotal role in preventing this problem These key/significant proteins can be identified by using modern proteomics and bioinformatics approaches for different diseases [13,14,15] including cutaneous leishmaniasis caused by L. major. The present study aims to analyze some topological properties including degree and betweenness centrality related to protein- protein interaction networks of L. major in order to identify hub-bottleneck proteins which can be recommended for new potential drug targets in this parasite. Protein-protein Interaction network analysis is a suitable tool to discover novel drug targets for leishmania major To this aim, gene and protein expression data is used for instructing protein network and the key proteins are highlighted. These key hub proteins could be a suitable and helpful potential for drug targets and treating leishmaniasis by considering their validation. [GMJ.2018;7:e1129] DOI:10.22086/gmj.v0i0.1129

Methods

Results

Discussion

Conclusion