Inferring Transmission Bottleneck Size from Viral Sequence Data Using a Novel Haplotype Reconstruction Method.
Journal of virology
American Society for Microbiology
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Ghafari, M., Lumby, C. K., Weissman, D. B., & Illingworth, C. (2020). Inferring Transmission Bottleneck Size from Viral Sequence Data Using a Novel Haplotype Reconstruction Method.. Journal of virology, 94 (13)https://doi.org/10.1128/jvi.00014-20
The transmission bottleneck is defined as the number of viral particles that transmit from one host to establish an infection in another. Genome sequence data has been used to evaluate the size of the transmission bottleneck between humans infected with the influenza virus, however, the methods used to make these estimates have some limitations. Specifically, viral allele frequencies, which form the basis of many calculations, may not fully capture a process which involves the transmission of entire viral genomes. Here we set out a novel approach for inferring viral transmission bottlenecks; our method combines an algorithm for haplotype reconstruction with maximum likelihood methods for bottleneck inference. This approach allows for rapid calculation, and performs well when applied to data from simulated transmission events; errors in the haplotype reconstruction step did not adversely affect inferences of the population bottleneck. Applied to data from a previous household transmission study of influenza A infection we confirm the result that the majority of transmission events involve a small number of viruses, albeit with slightly looser bottlenecks being inferred, with between 1 and 13 particles transmitted in the majority of cases. While influenza A transmission involves a tight population bottleneck, the bottleneck is not so tight as to universally prevent the transmission of within-host viral diversity.
Humans, Viruses, Influenza A virus, Sequence Analysis, DNA, Evolution, Molecular, Haplotypes, Genome, Viral, Models, Theoretical, Influenza, Human, Genetic Variation
University of Helsinki
Wellcome Trust (101239/Z/13/Z)
Isaac Newton Trust (Minute 18.23(i))
External DOI: https://doi.org/10.1128/jvi.00014-20
This record's URL: https://www.repository.cam.ac.uk/handle/1810/304339
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