Novel Technique Allows Genome Sequencing of Single Malaria Cells

A recently developed technique for analyzing the genome of a malaria parasite within a single red blood cell is expected to aid in the understanding of the molecular cell biology of these organisms and in the design of new drugs to prevent their growth and spread.

Investigators at the Texas Biomedical Research Institute (San Antonio, USA) combined advanced cell sorting technology and whole-genome amplification (WGA) to generate high-quality DNA samples from parasite-infected red blood cells (RBCs) for genotyping and next-generation sequencing. They optimized this approach through analysis of more than 260 single-cell assays, and quantified accuracy by decomposing mixtures of known parasite genotypes and obtaining highly accurate (> 99%) single-cell genotypes.

The investigators applied this validated approach directly to infections of two major malaria species, Plasmodium falciparum, for which long term culture is possible, and Plasmodium vivax, for which no long-term culture is feasible. They demonstrated that the single-cell genomics approach could be used to generate parasite genome sequences directly from patient blood in order to unravel the complexity of P. vivax and P. falciparum infections.

Malaria parasite infections are complex and often contain multiple different parasite genotypes and even different parasite species. "This has really limited our understanding of malaria parasite biology" said senior author Dr. Ian Cheeseman, a postdoctoral scientist in the genetics department of the Texas Biomedical Research Institute. “It is like trying to understand human genetics by making DNA from everyone in a village at once. The data is all jumbled up – what we really want is information from individuals. We are now able to look at malaria infections with incredible detail. This will help us understand how to best design drugs and vaccines to tackle this major global killer.”

The study describing the novel single-cell approach for genome sequencing was published in the May 8, 2014, online edition of the journal Genome Research.

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Texas Biomedical Research Institute