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Computational Evaluation of B-Cell Clone Sizes in Bulk Populations
Journal article   Open access   Peer reviewed

Computational Evaluation of B-Cell Clone Sizes in Bulk Populations

Aaron M. Rosenfeld, Wenzhao Meng, Dora Y. Chen, Bochao Zhang, Tomer Granot, Donna L. Farber, Uri Hershberg and Eline T. Luning Prak
Frontiers in immunology, v 9, pp 1472-1472
29 Jun 2018
PMID: 30008715
url
https://doi.org/10.3389/fimmu.2018.01472View
Published, Version of Record (VoR)CC BY V4.0 Open

Abstract

antibody B cell clone diversity immune repertoire immunoglobulin Immunology next generation sequencing
B cell clones expand and contract during adaptive immune responses and can persist or grow uncontrollably in lymphoproliferative disorders. One way to monitor and track B cell clones is to perform large-scale sampling of bulk cell populations, amplifying, and sequencing antibody gene rearrangements by next-generation sequencing (NGS). Here, we describe a series of computational approaches for estimating B cell clone size in NGS immune repertoire profiling data of antibody heavy chain gene rearrangements. We define three different measures of B cell clone size—copy numbers, instances, and unique sequences—and show how these measures can be used to rank clones, analyze their diversity, and study their distribution within and between individuals. We provide a detailed, step-by-step procedure for performing these analyses using two different data sets of spleen samples from human organ donors. In the first data set, 19 independently generated biological replicates from a single individual are analyzed for B cell clone size, diversity and sampling sufficiency for clonal overlap analysis. In the second data set, B cell clones are compared in eight different organ donors. We comment upon frequently encountered pitfalls and offer practical advice with alternative approaches. Overall, we provide a series of pragmatic analytical approaches and show how different clone size measures can be used to study the clonal landscape in bulk B cell immune repertoire profiling data.

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32 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Immunology
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