Resolving within-host malaria parasite diversity using single-cell sequencing

Nkhoma, S. C.; Trevino, S. G.; Gorena, K. M.; Nair, S.; Khoswe, S.; Jett, C.; Garcia, R.; Daniel, B.; Dia, A.; Terlouw, D. J.; Ward, S. A.; Anderson, T. J.; Cheeseman, I. H.

doi:10.1101/391268

bioRxiv · 10.1101/391268

Resolving within-host malaria parasite diversity using single-cell sequencing

Nkhoma, S. C.·Trevino, S. G.·Gorena, K. M.·Nair, S.·Khoswe, S.·Jett, C.·Garcia, R.·Daniel, B.·Dia, A.·Terlouw, D. J.·Ward, S. A.·Anderson, T. J.·Cheeseman, I. H.

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Abstract

Malaria patients can carry one or more clonal lineage of the parasite, Plasmodium falciparum, but the composition of these infections cannot be directly inferred from bulk sequence data. Well-defined, complete haplotypes at single-cell resolution are ideal for describing within-host population structure and unambiguously determining parasite diversity, transmission dynamics and recent ancestry but have not been analyzed on a large scale. We generated 485 near-complete single-cell genome sequences isolated from fifteen P. falciparum patients from Chikhwawa, Malawi, an area of intense malaria transmission. Matched single-cell and bulk genomic analyses revealed patients harbored up to seventeen unique lineages. Estimation of parasite relatedness within patients suggests superinfection by repeated mosquito bites is rarer than co-transmission of parasites from a single mosquito. Our single-cell analysis indicates strong barriers to establishment of new infections in malaria-infected patients and allows high resolution dissection of intra-host variation in malaria parasites.

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Nkhoma, S. C., Trevino, S. G., Gorena, K. M., Nair, S., Khoswe, S., Jett, C., Garcia, R., Daniel, B., Dia, A., Terlouw, D. J., Ward, S. A., Anderson, T. J., Cheeseman, I. H.. 2018-08-13. Resolving within-host malaria parasite diversity using single-cell sequencing. https://doi.org/10.1101/391268

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