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

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]

Identification of protein profile in metacyclic and amastigote-like stages of Leishmania tropica: a proteomic approach

“…Herein, we also investigated PPI network of differentially expressed proteins via bioinformatics approach. Since PPI network analysis is a powerful approach in categorization and ranking of the drug target candidate and potential biomarker for a certain disease (Chávez-Fumagalli et al 2018 ; Dashatan et al 2018 ; Flórez et al 2010 ), here the PPI network of the significant different regulated proteins are constructed (Fig. 4 ).…”

“…4 ). Topological analysis of the networks leads to rank of the nodes based on their centrality properties in network (Dashatan et al 2018 ; Jeong et al 2001 ). By degree centrality value using Cytohubba plugin in Cytoscape software, the top 10 node selected as important hub proteins.…”

“…Furthermore, enolase enzyme is available in secretome and leishmanial parasite surface. Based on the surface enolase, plasminogen receptor can probably play a role in virulence and invasiveness of parasites (Avilán et al 2011 ; Dashatan et al 2018 ). It must be pointed out that further investigations are required using western blotting or real time PCR to validate the results of this study.…”

“…L. major and L. tropica are the causative agents for cutaneous leishmaniasis in Iran and some of the neighboring countries (Ahmadi et al 2013 ; Ashrafmansouri et al 2015 ). Since the parasites regulate gene expression mainly at post-transcriptional stages, “Omics” approach including genomics, proteomics (Jardim et al 2018 ; Sundar and Singh 2018 ), metabolomics (Atan et al 2018 ) along with bioinformatics analysis (Dashatan et al 2018 ) is thought to yield critical insight into the mechanisms of stage differentiation, parasite biology, species differences, virulence and drug resistance (Amiri-Dashatan et al 2018 , 2020a ; Menezes et al 2013 ; Moreira et al 2014 ). In the field of the molecular differences between procyclic, metacyclic and amastigote forms, several investigation was reported the proteome of promastigotes and amastigotes forms of L. major , L. infantum , L. donovani and L. Mexicana .…”

Assessment of Immunological Effects of Low-Level Er: YAG Laser Radiation

“…The common hubs and bottlenecks are known as hub-bottlenecks that are considered the crucial central proteins. 12,13 Osteoblasts are known as multi-functional cells, and the critical roles of this type of cells in rapid periosteal bone formation and angiogenesis following the fracture are confirmed. 14 In the present study, data from a proteomics study by Niimi et al, entitled "Effects of low-level Er: YAG laser irradiation on proliferation and calcification of primary osteoblast-like cells isolated from rat calvaria", 15 were analyzed via network analysis to explore the possible critical proteins, especially the central dysregulated genes and biological terms.…”