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Limited predictability of amino acid substitutions in seasonal influenza viruses

View ORCID ProfilePierre Barrat-Charlaix, View ORCID ProfileJohn Huddleston, View ORCID ProfileTrevor Bedford, View ORCID ProfileRichard A. Neher
doi: https://doi.org/10.1101/2020.07.31.231100
Pierre Barrat-Charlaix
1Biozentrum, Universität Basel, Switzerland
2Swiss Institute of Bioinformatics, Basel, Switzerland
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  • ORCID record for Pierre Barrat-Charlaix
John Huddleston
3Molecular Cell Biology, University of Washington, Seattle, WA, USA
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Trevor Bedford
4Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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Richard A. Neher
1Biozentrum, Universität Basel, Switzerland
2Swiss Institute of Bioinformatics, Basel, Switzerland
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  • For correspondence: richard.neher@unibas.ch
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Abstract

Seasonal influenza viruses repeatedly infect humans in part because they rapidly change their antigenic properties and evade host immune responses, necessitating frequent updates of the vaccine composition. Accurate predictions of strains circulating in the future could therefore improve the vaccine match. Here, we studied the predictability of frequency dynamics and fixation of amino acid substitutions. Current frequency was the strongest predictor of eventual fixation, as expected in neutral evolution. Other properties, such as occurrence in previously characterized epitopes or high Local Branching Index (LBI) had little predictive power. Parallel evolution was found to be moderately predictive of fixation. While the LBI had little power to predict frequency dynamics, it was still successful at picking strains representative of future populations. The latter is due to a tendency of the LBI to be high for consensus-like sequences that are closer to the future than the average sequence. Simulations of models of adapting populations, in contrast, show clear signals of predictability. This indicates that the evolution of influenza HA and NA, while driven by strong selection pressure to change, is poorly described by common models of directional selection such as travelling fitness waves.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/PierreBarrat/FluPredictibility

Copyright 
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 4.0 International license.
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Posted July 31, 2020.
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Limited predictability of amino acid substitutions in seasonal influenza viruses
Pierre Barrat-Charlaix, John Huddleston, Trevor Bedford, Richard A. Neher
bioRxiv 2020.07.31.231100; doi: https://doi.org/10.1101/2020.07.31.231100
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Limited predictability of amino acid substitutions in seasonal influenza viruses
Pierre Barrat-Charlaix, John Huddleston, Trevor Bedford, Richard A. Neher
bioRxiv 2020.07.31.231100; doi: https://doi.org/10.1101/2020.07.31.231100

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