Genome-wide studies to identify markers of artemisinin-resistant malaria

Objectives

This project aims to identify parasite genes underlying artemisinin resistance, in an effort to develop tools to track resistant parasites and contain them before they spread globally. It proposes genome-wide association studies (GWAS) that aim to identify molecular markers that can be used to track and contain artemisinin-resistant parasites before they spread globally.

The work will be accomplished in two aims.

1. First, a dense panel of single nucleotide polymorphisms (SNPs) will be used to map regions of the P. falciparum genome that are associated with artemisinin resistance. To accomplish this, the research team will use an established SNP- calling pipeline to determine genotypes at ~421,000 SNPs from short-read sequencing data in parasites collected during completed trials of artemisinin efficacy, and will estimate the association between parasite genotypes and the amount of time it takes to reduce parasitemia by half following artemisinin treatment (i.e. parasite clearance half-life). Associations will be estimated in two independent sample sets, and meta-analysis will be performed to validate genomic regions associated with artemisinin resistance.
2. The research team will identify and prioritize candidate genes within genomic regions identified in Aim 1 and use next-generation sequencing data to identify polymorphisms within high-priority genes and their association with parasite clearance half-life.