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Inferring the immune response from repertoire sequencing

High-throughput sequencing of B- and T-cell receptors makes it possible to track immune repertoires across time, in different tissues, and in acute and chronic diseases or in healthy individuals. However, quantitative comparison between repertoires is confounded by variability in the read count of e...

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Autores principales: Puelma Touzel, Maximilian, Walczak, Aleksandra M., Mora, Thierry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213749/
https://www.ncbi.nlm.nih.gov/pubmed/32348312
http://dx.doi.org/10.1371/journal.pcbi.1007873
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author Puelma Touzel, Maximilian
Walczak, Aleksandra M.
Mora, Thierry
author_facet Puelma Touzel, Maximilian
Walczak, Aleksandra M.
Mora, Thierry
author_sort Puelma Touzel, Maximilian
collection PubMed
description High-throughput sequencing of B- and T-cell receptors makes it possible to track immune repertoires across time, in different tissues, and in acute and chronic diseases or in healthy individuals. However, quantitative comparison between repertoires is confounded by variability in the read count of each receptor clonotype due to sampling, library preparation, and expression noise. Here, we present a general Bayesian approach to disentangle repertoire variations from these stochastic effects. Using replicate experiments, we first show how to learn the natural variability of read counts by inferring the distributions of clone sizes as well as an explicit noise model relating true frequencies of clones to their read count. We then use that null model as a baseline to infer a model of clonal expansion from two repertoire time points taken before and after an immune challenge. Applying our approach to yellow fever vaccination as a model of acute infection in humans, we identify candidate clones participating in the response.
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spelling pubmed-72137492020-05-26 Inferring the immune response from repertoire sequencing Puelma Touzel, Maximilian Walczak, Aleksandra M. Mora, Thierry PLoS Comput Biol Research Article High-throughput sequencing of B- and T-cell receptors makes it possible to track immune repertoires across time, in different tissues, and in acute and chronic diseases or in healthy individuals. However, quantitative comparison between repertoires is confounded by variability in the read count of each receptor clonotype due to sampling, library preparation, and expression noise. Here, we present a general Bayesian approach to disentangle repertoire variations from these stochastic effects. Using replicate experiments, we first show how to learn the natural variability of read counts by inferring the distributions of clone sizes as well as an explicit noise model relating true frequencies of clones to their read count. We then use that null model as a baseline to infer a model of clonal expansion from two repertoire time points taken before and after an immune challenge. Applying our approach to yellow fever vaccination as a model of acute infection in humans, we identify candidate clones participating in the response. Public Library of Science 2020-04-29 /pmc/articles/PMC7213749/ /pubmed/32348312 http://dx.doi.org/10.1371/journal.pcbi.1007873 Text en © 2020 Puelma Touzel et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://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
Puelma Touzel, Maximilian
Walczak, Aleksandra M.
Mora, Thierry
Inferring the immune response from repertoire sequencing
title Inferring the immune response from repertoire sequencing
title_full Inferring the immune response from repertoire sequencing
title_fullStr Inferring the immune response from repertoire sequencing
title_full_unstemmed Inferring the immune response from repertoire sequencing
title_short Inferring the immune response from repertoire sequencing
title_sort inferring the immune response from repertoire sequencing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213749/
https://www.ncbi.nlm.nih.gov/pubmed/32348312
http://dx.doi.org/10.1371/journal.pcbi.1007873
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