We quantify the VDJ recombination and somatic hypermutation processes in
human B-cells using probabilistic inference methods on high-throughput DNA
sequence repertoires of human B-cell receptor heavy chains. Our analysis
captures the statistical properties of the naive repertoire, first after its
initial generation via VDJ recombination and then after selection for
functionality. We also infer statistical properties of the somatic
hypermutation machinery (exclusive of subsequent effects of selection). Our
main results are the following: the B-cell repertoire is substantially more
diverse than T-cell repertoires, due to longer junctional insertions; sequences
that pass initial selection are distinguished by having a higher probability of
being generated in a VDJ recombination event; somatic hypermutations have a
non-uniform distribution along the V gene that is well explained by an
independent site model for the sequence context around the hypermutation site.
%0 Generic
%1 elhanati2015inferring
%A Elhanati, Yuval
%A Sethna, Zachary
%A Marcou, Quentin
%A Callan Jr., Curtis G.
%A Mora, Thierry
%A Walczak, Aleksandra M.
%D 2015
%K B_cells VDJ context-dependent-mutation hypermutability somatic_mutation
%T Inferring processes underlying B-cell repertoire diversity
%U http://arxiv.org/abs/1502.03136
%X We quantify the VDJ recombination and somatic hypermutation processes in
human B-cells using probabilistic inference methods on high-throughput DNA
sequence repertoires of human B-cell receptor heavy chains. Our analysis
captures the statistical properties of the naive repertoire, first after its
initial generation via VDJ recombination and then after selection for
functionality. We also infer statistical properties of the somatic
hypermutation machinery (exclusive of subsequent effects of selection). Our
main results are the following: the B-cell repertoire is substantially more
diverse than T-cell repertoires, due to longer junctional insertions; sequences
that pass initial selection are distinguished by having a higher probability of
being generated in a VDJ recombination event; somatic hypermutations have a
non-uniform distribution along the V gene that is well explained by an
independent site model for the sequence context around the hypermutation site.
@misc{elhanati2015inferring,
abstract = {We quantify the VDJ recombination and somatic hypermutation processes in
human B-cells using probabilistic inference methods on high-throughput DNA
sequence repertoires of human B-cell receptor heavy chains. Our analysis
captures the statistical properties of the naive repertoire, first after its
initial generation via VDJ recombination and then after selection for
functionality. We also infer statistical properties of the somatic
hypermutation machinery (exclusive of subsequent effects of selection). Our
main results are the following: the B-cell repertoire is substantially more
diverse than T-cell repertoires, due to longer junctional insertions; sequences
that pass initial selection are distinguished by having a higher probability of
being generated in a VDJ recombination event; somatic hypermutations have a
non-uniform distribution along the V gene that is well explained by an
independent site model for the sequence context around the hypermutation site.},
added-at = {2015-02-25T02:09:26.000+0100},
author = {Elhanati, Yuval and Sethna, Zachary and Marcou, Quentin and Callan Jr., Curtis G. and Mora, Thierry and Walczak, Aleksandra M.},
biburl = {https://www.bibsonomy.org/bibtex/2ce226a785494b345cdd6d4608b137330/peter.ralph},
interhash = {7c704f2c860f2a953322d9ced2f3567e},
intrahash = {ce226a785494b345cdd6d4608b137330},
keywords = {B_cells VDJ context-dependent-mutation hypermutability somatic_mutation},
note = {cite arxiv:1502.03136},
timestamp = {2015-02-25T02:09:26.000+0100},
title = {Inferring processes underlying {B}-cell repertoire diversity},
url = {http://arxiv.org/abs/1502.03136},
year = 2015
}