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Genotyping genetically heterogeneous Cyclospora cayetanensis infections to complement epidemiological case linkage

  • Joel L. N. Barratt (a1) (a2), Subin Park (a1) (a2), Fernanda S. Nascimento (a1), Jessica Hofstetter (a1) (a2), Mateusz Plucinski (a3), Shannon Casillas (a1), Richard S. Bradbury (a1), Michael J. Arrowood (a4), Yvonne Qvarnstrom (a1) and Eldin Talundzic (a3)...

Abstract

Sexually reproducing pathogens such as Cyclospora cayetanensis often produce genetically heterogeneous infections where the number of unique sequence types detected at any given locus varies depending on which locus is sequenced. The genotypes assigned to these infections quickly become complex when additional loci are analysed. This genetic heterogeneity confounds the utility of traditional sequence-typing and phylogenetic approaches for aiding epidemiological trace-back, and requires new methods to address this complexity. Here, we describe an ensemble of two similarity-based classification algorithms, including a Bayesian and heuristic component that infer the relatedness of C. cayetanensis infections. The ensemble requires a set of haplotypes as input and assigns arbitrary distances to specimen pairs reflecting their most likely relationships. The approach was applied to data generated from a test cohort of 88 human fecal specimens containing C. cayetanensis, including 30 from patients whose infections were associated with epidemiologically defined outbreak clusters of cyclosporiasis. The ensemble assigned specimens to plausible clusters of genetically related infections despite their complex haplotype composition. These relationships were corroborated by a significant number of epidemiological linkages (P < 0.0001) suggesting the ensemble's utility for aiding epidemiological trace-back investigations of cyclosporiasis.

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Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike licence (http://creativecommons.org/licenses/by-nc-sa/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the same Creative Commons licence is included and the original work is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use.

Corresponding author

Author for correspondence: Joel L. N. Barratt, E-mail: jbarratt@cdc.gov; joelbarratt43@gmail.com

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Authors contributed equally.

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References

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