Computational analysis of transcriptome and metabolic pathways of malaria parasite Plasmodium falciparum

Abstract

The drug resistance in malaria parasites is increasingly emerging, so it is important to discover and develop alternative anti-malarial agents against both new and established drug targets. In this study, a comprehensive computational approach was used to derive potential therapeutic targets for P. falciparum using RNA-seq data set. The differential expression of genes, functional and pathway enrichment analyses of P. falciparum has been apprized in detail. The present study results suggested that PF3D7_0705600, PF3D7_1207100, PF3D7_0508100, PF3D7_1126700, and PF3D7_1234300 hub genes might serve as putative targets for drug designing. These hub genes are showing less mutation and no similarity with human proteins. In addition, the gene finding strategies of this study resulted into a database of different identifiers. This developed database tool (www.cdkd.org/pfidmap/) provides easy mapping of different identifiers related to P. falciparum. Functional analysis of the nsSNPs of identified hub genes was undertaken to predict deleterious mutations using various computational approaches and a database has been developed to demonstrate the analysis done by PROVEAN, SIFT, PredictSNP and NetSurfP software, which is available online at www.cdkd.org/pfsnp/. Moreover, the effect of deleterious mutations in glycosylphosphatidylinositol transamidase (GPI-T) subunit GPI8p has been investigated, which could be considered as a potential drug target primarily because of its crucial role in the GPI anchor biosynthesis pathway for the development as well as survival of the parasite. Thiamine phosphate synthase (PfThiE), an essential metabolic gene in the thiamine biosynthesis pathway is also studied and potential inhibitors were identified through dockingbased virtual screening along with drug-likeness and ADMET analysis to derive therapeutic targets for P. falciparum. Therefore, hub genes identified in this research, GPI8p and PfThiE may be considered as potential drug targets for P. falciparum.