Characterization of Within-Host Plasmodium falciparum Diversity Using Next-Generation Sequence Data


Auburn, S; Campino, S; Miotto, O; Djimde, AA; Zongo, I; Manske, M; Maslen, G; Mangano, V; Alcock, D; MacInnis, B; Rockett, KA; Clark, TG; Doumbo, OK; Ouedraogo, JB; Kwiatkowski, DP; (2012) Characterization of Within-Host Plasmodium falciparum Diversity Using Next-Generation Sequence Data. PLoS One, 7 (2). ISSN 1932-6203 DOI: 10.1371/journal.pone.0032891

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Abstract

Our understanding of the composition of multi-clonal malarial infections and the epidemiological factors which shape their diversity remain poorly understood. Traditionally within-host diversity has been defined in terms of the multiplicity of infection (MOI) derived by PCR-based genotyping. Massively parallel, single molecule sequencing technologies now enable individual read counts to be derived on genome-wide datasets facilitating the development of new statistical approaches to describe within-host diversity. In this class of measures the FWS metric characterizes within-host diversity and its relationship to population level diversity. Utilizing P. falciparum field isolates from patients in West Africa we here explore the relationship between the traditional MOI and F-WS approaches. F-WS statistics were derived from read count data at 86,158 SNPs in 64 samples sequenced on the Illumina GA platform. MOI estimates were derived by PCR at the msp-1 and -2 loci. Significant correlations were observed between the two measures, particularly with the msp-1 locus (P=5.92x10(-5)). The F-WS metric should be more robust than the PCR-based approach owing to reduced sensitivity to potential locus-specific artifacts. Furthermore the F-WS metric captures information on a range of parameters which influence out-crossing risk including the number of clones (MOI), their relative proportions and genetic divergence. This approach should provide novel insights into the factors which correlate with, and shape within-host diversity.

Item Type: Article
Keywords: genetically diverse, malaria infections, clinical malaria, drug-treatment, genome, evolution, virulence, parasites, children, surface
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: Malaria Centre
PubMed ID: 22393456
Web of Science ID: 303003500111
URI: http://researchonline.lshtm.ac.uk/id/eprint/62646

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