Network Analysis of the Protein-Protein Interaction of Insecticide Resistance in Anopheles gambiae

The increased resistance to currently existing insecticides has called for research to fully grasp the underlying mechanisms by which Anopheles evade insecticides entirely. Analysis of insecticide resistance networks can help identify central genes, functional modules, and functional annotations of candidate genes. This will enable the development of novel control measures for malaria, one of the deadliest diseases affecting millions of people in Africa. In this study, the Anopheles gambiae insecticides resistance protein-protein interaction network (PPIN) was constructed from genes retrieved from various studies using STRING and Cytoscape. The retrieved genes are insecticide-resistant genes identified by different experimental research. Thus, the study aims to elucidate the roles of these genes and identify other genes that may influence insecticide resistance by interacting with the retrieved genes. The network underwent topology and clustering analysis using several Cytoscape in-built algorithms. Gene ontology and pathway enrichment analysis were conducted to identify significant processes and pathways linked to resistance. The result obtained comprises 224 proteins (nodes) and 2115 interactions (edges) within the constructed network. Furthermore, essential candidate target proteins, such as AGAP004581, AGAP002945, GSTE2, GSTE1, and GSTD3, were identified as hub protein associated with resistance in A. gambiae. Most of these were found to be linked with critical pathways, such as protein processing, glutathione and cytochrome P450s. The identified genes, particularly AGAP004581 and AGAP002945, which were identified for the first time, will serve as potential targets for developing new insecticides. Overall, the study will contribute to the knowledge base required to facilitate the development of novel, target-specific insecticides. These findings can potentially guide future research efforts aimed at curtailing the challenges posed by insecticide resistance and contributing to combating malaria.