Estimating T-cell repertoire diversity: limitations of classical estimators and a new approach
File(s)
Published version
Author(s)
Asquith, RE
Laydon, D
Bangham, C
Type
Journal Article
Abstract
A highly diverse T-cell receptor (TCR) repertoire is a fundamental property of an effective immune system, and is associated with efficient control of viral infections and other pathogens. However, direct measurement of total TCR diversity is impossible. The diversity is high and the frequency distribution of individual TCRs is heavily skewed; the diversity therefore cannot be captured in a blood sample. Consequently, estimators of the total number of TCR clonotypes that are present in the individual, in addition to those observed, are essential. This is analogous to the ‘unseen species problem’ in ecology. We review the diversity (species richness) estimators that have been applied to T-cell repertoires and the methods used to validate these estimators. We show that existing approaches have significant shortcomings, and frequently underestimate true TCR diversity. We highlight our recently developed estimator, DivE, which can accurately estimate diversity across a range of immunological and biological systems.
Date Issued
2015-07-06
Date Acceptance
2015-05-04
Citation
Philosophical Transactions of the Royal Society B: Biological Sciences, 2015, 370 (1675)
ISSN
1471-2970
Publisher
The Royal Society
Journal / Book Title
Philosophical Transactions of the Royal Society B: Biological Sciences
Volume
370
Issue
1675
Copyright Statement
© 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution
License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original
author and source are credited.
License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original
author and source are credited.
License URL
Publication Status
Published
Article Number
20140291