An Expectation Maximization Approach to Estimate Malaria Haplotype Frequencies in Multiply Infected Children
Foulkes Andrea S,
Yucel Recai M. and
Rich Stephen M.
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Li Xiaohong: University of Massachusetts, Amherst
Foulkes Andrea S: University of Massachusetts, Amherst
Yucel Recai M.: University of Massachusetts, Amherst
Rich Stephen M.: University of Massachusetts, Amherst
Statistical Applications in Genetics and Molecular Biology, 2007, vol. 6, issue 1, 1-19
Characterizing genetic variability in the human pathogenic Plasmodium species, the group of parasites that cause Malaria, may have broad global health implications. Specifically, discerning the combinations of mutations that lead to viable parasites and the population level frequencies of these clonal sequences will allow for targeted vaccine development and individualized treatment choices. This presents an analytical challenge, however, since haplotypic phase (i.e. the alignment of bases on a single DNA strand) is generally unobservable in multiply infected individuals. This manuscript describes an expectation maximization (EM) approach to maximum likelihood estimation of haplotype frequencies in this missing data setting. The approach is applied to a cohort of N=341 malaria infected children in Uganda, Cameroon and Sudan to characterize regional differences. A simulation study is also presented to characterize method performance and assess sensitivity to distributional assumptions.
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