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Exploring the impact of clonal definition on B-cell diversity: implications for the analysis of immune repertoires

The adaptive immune system has the extraordinary ability to produce a broad range of immunoglobulins that can bind a wide variety of antigens. During adaptive immune responses, activated B cells duplicate and undergo somatic hypermutation in their B-cell receptor (BCR) genes, resulting in clonal fam...

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Autores principales: Pelissier, Aurelien, Luo, Siyuan, Stratigopoulou, Maria, Guikema, Jeroen E. J., Rodríguez Martínez, María
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10150052/
https://www.ncbi.nlm.nih.gov/pubmed/37138881
http://dx.doi.org/10.3389/fimmu.2023.1123968
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author Pelissier, Aurelien
Luo, Siyuan
Stratigopoulou, Maria
Guikema, Jeroen E. J.
Rodríguez Martínez, María
author_facet Pelissier, Aurelien
Luo, Siyuan
Stratigopoulou, Maria
Guikema, Jeroen E. J.
Rodríguez Martínez, María
author_sort Pelissier, Aurelien
collection PubMed
description The adaptive immune system has the extraordinary ability to produce a broad range of immunoglobulins that can bind a wide variety of antigens. During adaptive immune responses, activated B cells duplicate and undergo somatic hypermutation in their B-cell receptor (BCR) genes, resulting in clonal families of diversified B cells that can be related back to a common ancestor. Advances in high-throughput sequencing technologies have enabled the high-throughput characterization of B-cell repertoires, however, the accurate identification of clonally related BCR sequences remains a major challenge. In this study, we compare three different clone identification methods on both simulated and experimental data, and investigate their impact on the characterization of B-cell diversity. We observe that different methods lead to different clonal definitions, which affects the quantification of clonal diversity in repertoire data. Our analyses show that direct comparisons between clonal clusterings and clonal diversity of different repertoires should be avoided if different clone identification methods were used to define the clones. Despite this variability, the diversity indices inferred from the repertoires’ clonal characterization across samples show similar patterns of variation regardless of the clonal identification method used. We find the Shannon entropy to be the most robust in terms of the variability of diversity rank across samples. Our analysis also suggests that the traditional germline gene alignment-based method for clonal identification remains the most accurate when the complete information about the sequence is known, but that alignment-free methods may be preferred for shorter sequencing read lengths. We make our implementation freely available as a Python library cdiversity.
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spelling pubmed-101500522023-05-02 Exploring the impact of clonal definition on B-cell diversity: implications for the analysis of immune repertoires Pelissier, Aurelien Luo, Siyuan Stratigopoulou, Maria Guikema, Jeroen E. J. Rodríguez Martínez, María Front Immunol Immunology The adaptive immune system has the extraordinary ability to produce a broad range of immunoglobulins that can bind a wide variety of antigens. During adaptive immune responses, activated B cells duplicate and undergo somatic hypermutation in their B-cell receptor (BCR) genes, resulting in clonal families of diversified B cells that can be related back to a common ancestor. Advances in high-throughput sequencing technologies have enabled the high-throughput characterization of B-cell repertoires, however, the accurate identification of clonally related BCR sequences remains a major challenge. In this study, we compare three different clone identification methods on both simulated and experimental data, and investigate their impact on the characterization of B-cell diversity. We observe that different methods lead to different clonal definitions, which affects the quantification of clonal diversity in repertoire data. Our analyses show that direct comparisons between clonal clusterings and clonal diversity of different repertoires should be avoided if different clone identification methods were used to define the clones. Despite this variability, the diversity indices inferred from the repertoires’ clonal characterization across samples show similar patterns of variation regardless of the clonal identification method used. We find the Shannon entropy to be the most robust in terms of the variability of diversity rank across samples. Our analysis also suggests that the traditional germline gene alignment-based method for clonal identification remains the most accurate when the complete information about the sequence is known, but that alignment-free methods may be preferred for shorter sequencing read lengths. We make our implementation freely available as a Python library cdiversity. Frontiers Media S.A. 2023-04-17 /pmc/articles/PMC10150052/ /pubmed/37138881 http://dx.doi.org/10.3389/fimmu.2023.1123968 Text en Copyright © 2023 Pelissier, Luo, Stratigopoulou, Guikema and Rodríguez Martínez https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Pelissier, Aurelien
Luo, Siyuan
Stratigopoulou, Maria
Guikema, Jeroen E. J.
Rodríguez Martínez, María
Exploring the impact of clonal definition on B-cell diversity: implications for the analysis of immune repertoires
title Exploring the impact of clonal definition on B-cell diversity: implications for the analysis of immune repertoires
title_full Exploring the impact of clonal definition on B-cell diversity: implications for the analysis of immune repertoires
title_fullStr Exploring the impact of clonal definition on B-cell diversity: implications for the analysis of immune repertoires
title_full_unstemmed Exploring the impact of clonal definition on B-cell diversity: implications for the analysis of immune repertoires
title_short Exploring the impact of clonal definition on B-cell diversity: implications for the analysis of immune repertoires
title_sort exploring the impact of clonal definition on b-cell diversity: implications for the analysis of immune repertoires
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10150052/
https://www.ncbi.nlm.nih.gov/pubmed/37138881
http://dx.doi.org/10.3389/fimmu.2023.1123968
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