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Title: Characterization of within-host plasmodium falciparum diversity using next-generation sequence data
Authors: Sarah Auburn
Susana Campino
Olivo Miotto
Abdoulaye A. Djimde
Issaka Zongo
Magnus Manske
Gareth Maslen
Valentina Mangano
Daniel Alcock
Bronwyn MacInnis
Kirk A. Rockett
Taane G. Clark
Ogobara K. Doumbo
Jean Bosco Ouédraogo
Dominic P. Kwiatkowski
Wellcome Trust Sanger Institute
Menzies School of Health Research
University of Oxford
Mahidol University
University of Bamako Faculty of Medicine, Pharmacy and Odonto-Stomatology
Institut de Recherche en Sciences de la Santé
Universita degli Studi di Roma La Sapienza
Wellcome Trust Centre for Human Genetics
London School of Hygiene & Tropical Medicine
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 29-Feb-2012
Citation: PLoS ONE. Vol.7, No.2 (2012)
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 F WS 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 = 5.92×10 -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. © 2012 Auburn et al.
ISSN: 19326203
Appears in Collections:Scopus 2011-2015

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