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Estimating the overlap between two malaria parasites' var repertoires

View ORCID ProfileDaniel B Larremore
doi: https://doi.org/10.1101/343152
Daniel B Larremore
University of Colorado Boulder
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Abstract

Measuring the overlap between the var gene repertoires of two Plasmodium falciparum parasites is, in principle, easy. Each parasite genome contains a repertoire of approximately 60 var genes, so upon fully sequencing both parasites' genomes, the number of shared var sequences can be directly counted. In practice, however, only a fraction of each parasite's var repertoire is likely to be sampled due to the difficulties of whole-genome sequencing for var genes and the stochastic sample provided by PCR techniques. Although a method exists for quantifying repertoire overlap under these subsampled conditions, its bias is well documented and the uncertainty of its estimates cannot be quantified. Here we derive and validate a method to rigorously estimate the repertoire overlap between two parasites from the overlap of their subsampled repertoires. By solving a Bayesian inference problem, this method takes into account the rates of subsampling and produces unbiased and Bayes-optimal estimates of overlap. In addition, it provides a natural framework for computing the uncertainty of its estimates, and can be used in laboratory planning by quantifying the tradeoff between sequencing effort and uncertainty.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted June 11, 2018.
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Estimating the overlap between two malaria parasites' var repertoires
Daniel B Larremore
bioRxiv 343152; doi: https://doi.org/10.1101/343152
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Estimating the overlap between two malaria parasites' var repertoires
Daniel B Larremore
bioRxiv 343152; doi: https://doi.org/10.1101/343152

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