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Phylogenetic analysis of migration, differentiation, and class switching in B cells
B cells undergo rapid mutation and selection for antibody binding affinity when producing antibodies capable of neutralizing pathogens. This evolutionary process can be intermixed with migration between tissues, differentiation between cellular subsets, and switching between functional isotypes. B c...
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/PMC9037912/ https://www.ncbi.nlm.nih.gov/pubmed/35468128 http://dx.doi.org/10.1371/journal.pcbi.1009885 |
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author | Hoehn, Kenneth B. Pybus, Oliver G. Kleinstein, Steven H. |
author_facet | Hoehn, Kenneth B. Pybus, Oliver G. Kleinstein, Steven H. |
author_sort | Hoehn, Kenneth B. |
collection | PubMed |
description | B cells undergo rapid mutation and selection for antibody binding affinity when producing antibodies capable of neutralizing pathogens. This evolutionary process can be intermixed with migration between tissues, differentiation between cellular subsets, and switching between functional isotypes. B cell receptor (BCR) sequence data has the potential to elucidate important information about these processes. However, there is currently no robust, generalizable framework for making such inferences from BCR sequence data. To address this, we develop three parsimony-based summary statistics to characterize migration, differentiation, and isotype switching along B cell phylogenetic trees. We use simulations to demonstrate the effectiveness of this approach. We then use this framework to infer patterns of cellular differentiation and isotype switching from high throughput BCR sequence datasets obtained from patients in a study of HIV infection and a study of food allergy. These methods are implemented in the R package dowser, available at https://dowser.readthedocs.io. |
format | Online Article Text |
id | pubmed-9037912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-90379122022-04-26 Phylogenetic analysis of migration, differentiation, and class switching in B cells Hoehn, Kenneth B. Pybus, Oliver G. Kleinstein, Steven H. PLoS Comput Biol Research Article B cells undergo rapid mutation and selection for antibody binding affinity when producing antibodies capable of neutralizing pathogens. This evolutionary process can be intermixed with migration between tissues, differentiation between cellular subsets, and switching between functional isotypes. B cell receptor (BCR) sequence data has the potential to elucidate important information about these processes. However, there is currently no robust, generalizable framework for making such inferences from BCR sequence data. To address this, we develop three parsimony-based summary statistics to characterize migration, differentiation, and isotype switching along B cell phylogenetic trees. We use simulations to demonstrate the effectiveness of this approach. We then use this framework to infer patterns of cellular differentiation and isotype switching from high throughput BCR sequence datasets obtained from patients in a study of HIV infection and a study of food allergy. These methods are implemented in the R package dowser, available at https://dowser.readthedocs.io. Public Library of Science 2022-04-25 /pmc/articles/PMC9037912/ /pubmed/35468128 http://dx.doi.org/10.1371/journal.pcbi.1009885 Text en © 2022 Hoehn 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 Hoehn, Kenneth B. Pybus, Oliver G. Kleinstein, Steven H. Phylogenetic analysis of migration, differentiation, and class switching in B cells |
title | Phylogenetic analysis of migration, differentiation, and class switching in B cells |
title_full | Phylogenetic analysis of migration, differentiation, and class switching in B cells |
title_fullStr | Phylogenetic analysis of migration, differentiation, and class switching in B cells |
title_full_unstemmed | Phylogenetic analysis of migration, differentiation, and class switching in B cells |
title_short | Phylogenetic analysis of migration, differentiation, and class switching in B cells |
title_sort | phylogenetic analysis of migration, differentiation, and class switching in b cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037912/ https://www.ncbi.nlm.nih.gov/pubmed/35468128 http://dx.doi.org/10.1371/journal.pcbi.1009885 |
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