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Assessing in vivo mutation frequencies and creating a high-resolution genome-wide map of fitness costs of Hepatitis C virus
Like many viruses, Hepatitis C Virus (HCV) has a high mutation rate, which helps the virus adapt quickly, but mutations come with fitness costs. Fitness costs can be studied by different approaches, such as experimental or frequency-based approaches. The frequency-based approach is particularly usef...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9113599/ https://www.ncbi.nlm.nih.gov/pubmed/35500034 http://dx.doi.org/10.1371/journal.pgen.1010179 |
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author | Tisthammer, Kaho H. Solis, Caroline Orcales, Faye Nzerem, Madu Winstead, Ryan Dong, Weiyan Joy, Jeffrey B. Pennings, Pleuni S. |
author_facet | Tisthammer, Kaho H. Solis, Caroline Orcales, Faye Nzerem, Madu Winstead, Ryan Dong, Weiyan Joy, Jeffrey B. Pennings, Pleuni S. |
author_sort | Tisthammer, Kaho H. |
collection | PubMed |
description | Like many viruses, Hepatitis C Virus (HCV) has a high mutation rate, which helps the virus adapt quickly, but mutations come with fitness costs. Fitness costs can be studied by different approaches, such as experimental or frequency-based approaches. The frequency-based approach is particularly useful to estimate in vivo fitness costs, but this approach works best with deep sequencing data from many hosts are. In this study, we applied the frequency-based approach to a large dataset of 195 patients and estimated the fitness costs of mutations at 7957 sites along the HCV genome. We used beta regression and random forest models to better understand how different factors influenced fitness costs. Our results revealed that costs of nonsynonymous mutations were three times higher than those of synonymous mutations, and mutations at nucleotides A or T had higher costs than those at C or G. Genome location had a modest effect, with lower costs for mutations in HVR1 and higher costs for mutations in Core and NS5B. Resistance mutations were, on average, costlier than other mutations. Our results show that in vivo fitness costs of mutations can be site and virus specific, reinforcing the utility of constructing in vivo fitness cost maps of viral genomes. |
format | Online Article Text |
id | pubmed-9113599 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-91135992022-05-18 Assessing in vivo mutation frequencies and creating a high-resolution genome-wide map of fitness costs of Hepatitis C virus Tisthammer, Kaho H. Solis, Caroline Orcales, Faye Nzerem, Madu Winstead, Ryan Dong, Weiyan Joy, Jeffrey B. Pennings, Pleuni S. PLoS Genet Research Article Like many viruses, Hepatitis C Virus (HCV) has a high mutation rate, which helps the virus adapt quickly, but mutations come with fitness costs. Fitness costs can be studied by different approaches, such as experimental or frequency-based approaches. The frequency-based approach is particularly useful to estimate in vivo fitness costs, but this approach works best with deep sequencing data from many hosts are. In this study, we applied the frequency-based approach to a large dataset of 195 patients and estimated the fitness costs of mutations at 7957 sites along the HCV genome. We used beta regression and random forest models to better understand how different factors influenced fitness costs. Our results revealed that costs of nonsynonymous mutations were three times higher than those of synonymous mutations, and mutations at nucleotides A or T had higher costs than those at C or G. Genome location had a modest effect, with lower costs for mutations in HVR1 and higher costs for mutations in Core and NS5B. Resistance mutations were, on average, costlier than other mutations. Our results show that in vivo fitness costs of mutations can be site and virus specific, reinforcing the utility of constructing in vivo fitness cost maps of viral genomes. Public Library of Science 2022-05-02 /pmc/articles/PMC9113599/ /pubmed/35500034 http://dx.doi.org/10.1371/journal.pgen.1010179 Text en © 2022 Tisthammer et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Tisthammer, Kaho H. Solis, Caroline Orcales, Faye Nzerem, Madu Winstead, Ryan Dong, Weiyan Joy, Jeffrey B. Pennings, Pleuni S. Assessing in vivo mutation frequencies and creating a high-resolution genome-wide map of fitness costs of Hepatitis C virus |
title | Assessing in vivo mutation frequencies and creating a high-resolution genome-wide map of fitness costs of Hepatitis C virus |
title_full | Assessing in vivo mutation frequencies and creating a high-resolution genome-wide map of fitness costs of Hepatitis C virus |
title_fullStr | Assessing in vivo mutation frequencies and creating a high-resolution genome-wide map of fitness costs of Hepatitis C virus |
title_full_unstemmed | Assessing in vivo mutation frequencies and creating a high-resolution genome-wide map of fitness costs of Hepatitis C virus |
title_short | Assessing in vivo mutation frequencies and creating a high-resolution genome-wide map of fitness costs of Hepatitis C virus |
title_sort | assessing in vivo mutation frequencies and creating a high-resolution genome-wide map of fitness costs of hepatitis c virus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9113599/ https://www.ncbi.nlm.nih.gov/pubmed/35500034 http://dx.doi.org/10.1371/journal.pgen.1010179 |
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