Two fitness inference schemes compared using allele frequencies from 1,068,391 sequences sampled in the UK during the COVID-19 pandemic

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Hauptverfasser: Zeng, Hong-Li, Yang, Cheng-Long, Jing, Bo, Barton, John, Aurell, Erik
Format: Preprint
Veröffentlicht: 2024
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author Zeng, Hong-Li
Yang, Cheng-Long
Jing, Bo
Barton, John
Aurell, Erik
author_facet Zeng, Hong-Li
Yang, Cheng-Long
Jing, Bo
Barton, John
Aurell, Erik
contents Throughout the course of the SARS-CoV-2 pandemic, genetic variation has contributed to the spread and persistence of the virus. For example, various mutations have allowed SARS-CoV-2 to escape antibody neutralization or to bind more strongly to the receptors that it uses to enter human cells. Here, we compared two methods that estimate the fitness effects of viral mutations using the abundant sequence data gathered over the course of the pandemic. Both approaches are grounded in population genetics theory but with different assumptions. One approach, tQLE, features an epistatic fitness landscape and assumes that alleles are nearly in linkage equilibrium. Another approach, MPL, assumes a simple, additive fitness landscape, but allows for any level of correlation between alleles. We characterized differences in the distributions of fitness values inferred by each approach and in the ranks of fitness values that they assign to sequences across time. We find that in a large fraction of weeks the two methods are in good agreement as to their top-ranked sequences, i.e., as to which sequences observed that week are most fit. We also find that agreement between ranking of sequences varies with genetic unimodality in the population in a given week.
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id arxiv_https___arxiv_org_abs_2403_14202
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publishDate 2024
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spellingShingle Two fitness inference schemes compared using allele frequencies from 1,068,391 sequences sampled in the UK during the COVID-19 pandemic
Zeng, Hong-Li
Yang, Cheng-Long
Jing, Bo
Barton, John
Aurell, Erik
Populations and Evolution
Quantitative Methods
Throughout the course of the SARS-CoV-2 pandemic, genetic variation has contributed to the spread and persistence of the virus. For example, various mutations have allowed SARS-CoV-2 to escape antibody neutralization or to bind more strongly to the receptors that it uses to enter human cells. Here, we compared two methods that estimate the fitness effects of viral mutations using the abundant sequence data gathered over the course of the pandemic. Both approaches are grounded in population genetics theory but with different assumptions. One approach, tQLE, features an epistatic fitness landscape and assumes that alleles are nearly in linkage equilibrium. Another approach, MPL, assumes a simple, additive fitness landscape, but allows for any level of correlation between alleles. We characterized differences in the distributions of fitness values inferred by each approach and in the ranks of fitness values that they assign to sequences across time. We find that in a large fraction of weeks the two methods are in good agreement as to their top-ranked sequences, i.e., as to which sequences observed that week are most fit. We also find that agreement between ranking of sequences varies with genetic unimodality in the population in a given week.
title Two fitness inference schemes compared using allele frequencies from 1,068,391 sequences sampled in the UK during the COVID-19 pandemic
topic Populations and Evolution
Quantitative Methods
url https://arxiv.org/abs/2403.14202