Genomic and Transcriptomic Analysis for Identification of Genes and Interlinked Pathways Mediating Artemisinin Resistance in Leishmania donovani.

Genes
Sushmita GhoshRuchi Singh

Abstract

Current therapy for visceral leishmaniasis (VL), compromised by drug resistance, toxicity, and high cost, demands for more effective, safer, and low-cost drugs. Artemisinin has been found to be an effectual drug alternative in experimental models of leishmaniasis. Comparative genome and transcriptome analysis of in vitro-adapted artesunate-resistant (K133AS-R) and -sensitive wild-type (K133WT) Leishmania donovani parasites was carried out using next-generation sequencing and single-color DNA microarray technology, respectively, to identify genes and interlinked pathways contributing to drug resistance. Whole-genome sequence analysis of K133WT vs. K133AS-R parasites revealed substantial variation among the two and identified 240 single nucleotide polymorphisms (SNPs), 237 insertion deletions (InDels), 616 copy number variations (CNVs) (377 deletions and 239 duplications), and trisomy of chromosome 12 in K133AS-R parasites. Transcriptome analysis revealed differential expression of 208 genes (fold change ≥ 2) in K133AS-R parasites. Functional categorization and analysis of modulated genes of interlinked pathways pointed out plausible adaptations in K133AS-R parasites, such as (i) a dependency on lipid and amino acid metabolism fo...Continue Reading

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Datasets Mentioned

BETA
SRR12487478
SRR12487479
GSE118460

Methods Mentioned

BETA
chip
mechanical
PCR
Assay
Feature Extraction
electrophoresis
Fluorescence
glycosylation
Whole-Genome Sequencing

Software Mentioned

Web Gene Ontology Annotation Plot ( WEGO )
BWA
Bcf
SAM
Picard
SnpEff
BLASTx
Primer express
R
- MEM

Related Concepts