Inferring transmission bottleneck size from viral sequence data using a novel haplotype reconstruction method

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 have been used to evaluate the size of the transmission bottleneck between humans infected with the influenza virus; however, the methods use...

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Main Authors: Ghafari, M, Lumby, CK, Weissman, DB, Illingworth, CJR
Format: Journal article
Language:English
Published: American Society for Microbiology 2020
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author Ghafari, M
Lumby, CK
Weissman, DB
Illingworth, CJR
author_facet Ghafari, M
Lumby, CK
Weissman, DB
Illingworth, CJR
author_sort Ghafari, M
collection OXFORD
description 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 have 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.
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spelling oxford-uuid:2001f181-69fb-49f1-9e09-61964b50433c2022-03-26T11:25:12ZInferring transmission bottleneck size from viral sequence data using a novel haplotype reconstruction methodJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2001f181-69fb-49f1-9e09-61964b50433cEnglishSymplectic ElementsAmerican Society for Microbiology2020Ghafari, MLumby, CKWeissman, DBIllingworth, CJRThe transmission bottleneck is defined as the number of viral particles that transmit from one host to establish an infection in another. Genome sequence data have 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.
spellingShingle Ghafari, M
Lumby, CK
Weissman, DB
Illingworth, CJR
Inferring transmission bottleneck size from viral sequence data using a novel haplotype reconstruction method
title Inferring transmission bottleneck size from viral sequence data using a novel haplotype reconstruction method
title_full Inferring transmission bottleneck size from viral sequence data using a novel haplotype reconstruction method
title_fullStr Inferring transmission bottleneck size from viral sequence data using a novel haplotype reconstruction method
title_full_unstemmed Inferring transmission bottleneck size from viral sequence data using a novel haplotype reconstruction method
title_short Inferring transmission bottleneck size from viral sequence data using a novel haplotype reconstruction method
title_sort inferring transmission bottleneck size from viral sequence data using a novel haplotype reconstruction method
work_keys_str_mv AT ghafarim inferringtransmissionbottlenecksizefromviralsequencedatausinganovelhaplotypereconstructionmethod
AT lumbyck inferringtransmissionbottlenecksizefromviralsequencedatausinganovelhaplotypereconstructionmethod
AT weissmandb inferringtransmissionbottlenecksizefromviralsequencedatausinganovelhaplotypereconstructionmethod
AT illingworthcjr inferringtransmissionbottlenecksizefromviralsequencedatausinganovelhaplotypereconstructionmethod