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Alignment free identification of clones in B cell receptor repertoires

Following antigenic challenge, activated B cells rapidly expand and undergo somatic hypermutation, yielding groups of clonally related B cells with diversified immunoglobulin receptors. Inference of clonal relationships based on the receptor sequence is an essential step in many adaptive immune rece...

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Autores principales: Lindenbaum, Ofir, Nouri, Nima, Kluger, Yuval, Kleinstein, Steven H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913774/
https://www.ncbi.nlm.nih.gov/pubmed/33330933
http://dx.doi.org/10.1093/nar/gkaa1160
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author Lindenbaum, Ofir
Nouri, Nima
Kluger, Yuval
Kleinstein, Steven H
author_facet Lindenbaum, Ofir
Nouri, Nima
Kluger, Yuval
Kleinstein, Steven H
author_sort Lindenbaum, Ofir
collection PubMed
description Following antigenic challenge, activated B cells rapidly expand and undergo somatic hypermutation, yielding groups of clonally related B cells with diversified immunoglobulin receptors. Inference of clonal relationships based on the receptor sequence is an essential step in many adaptive immune receptor repertoire sequencing studies. These relationships are typically identified by a multi-step process that involves: (i) grouping sequences based on shared V and J gene assignments, and junction lengths and (ii) clustering these sequences using a junction-based distance. However, this approach is sensitive to the initial gene assignments, which are error-prone, and fails to identify clonal relatives whose junction length has changed through accumulation of indels. Through defining a translation-invariant feature space in which we cluster the sequences, we develop an alignment free clonal identification method that does not require gene assignments and is not restricted to a fixed junction length. This alignment free approach has higher sensitivity compared to a typical junction-based distance method without loss of specificity and PPV. While the alignment free procedure identifies clones that are broadly consistent with the junction-based distance method, it also identifies clones with characteristics (multiple V or J gene assignments or junction lengths) that are not detectable with the junction-based distance method.
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spelling pubmed-79137742021-03-03 Alignment free identification of clones in B cell receptor repertoires Lindenbaum, Ofir Nouri, Nima Kluger, Yuval Kleinstein, Steven H Nucleic Acids Res Methods Online Following antigenic challenge, activated B cells rapidly expand and undergo somatic hypermutation, yielding groups of clonally related B cells with diversified immunoglobulin receptors. Inference of clonal relationships based on the receptor sequence is an essential step in many adaptive immune receptor repertoire sequencing studies. These relationships are typically identified by a multi-step process that involves: (i) grouping sequences based on shared V and J gene assignments, and junction lengths and (ii) clustering these sequences using a junction-based distance. However, this approach is sensitive to the initial gene assignments, which are error-prone, and fails to identify clonal relatives whose junction length has changed through accumulation of indels. Through defining a translation-invariant feature space in which we cluster the sequences, we develop an alignment free clonal identification method that does not require gene assignments and is not restricted to a fixed junction length. This alignment free approach has higher sensitivity compared to a typical junction-based distance method without loss of specificity and PPV. While the alignment free procedure identifies clones that are broadly consistent with the junction-based distance method, it also identifies clones with characteristics (multiple V or J gene assignments or junction lengths) that are not detectable with the junction-based distance method. Oxford University Press 2020-12-16 /pmc/articles/PMC7913774/ /pubmed/33330933 http://dx.doi.org/10.1093/nar/gkaa1160 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Methods Online
Lindenbaum, Ofir
Nouri, Nima
Kluger, Yuval
Kleinstein, Steven H
Alignment free identification of clones in B cell receptor repertoires
title Alignment free identification of clones in B cell receptor repertoires
title_full Alignment free identification of clones in B cell receptor repertoires
title_fullStr Alignment free identification of clones in B cell receptor repertoires
title_full_unstemmed Alignment free identification of clones in B cell receptor repertoires
title_short Alignment free identification of clones in B cell receptor repertoires
title_sort alignment free identification of clones in b cell receptor repertoires
topic Methods Online
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913774/
https://www.ncbi.nlm.nih.gov/pubmed/33330933
http://dx.doi.org/10.1093/nar/gkaa1160
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