IgTreeZ, A Toolkit for Immunoglobulin Gene Lineage Tree-Based Analysis, Reveals CDR3s Are Crucial for Selection Analysis.

B cell receptor (BCR) B cell repertoire antibody immunoglobulin lineage tree somatic hypermutation (SHM)

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2022
Historique:
received: 26 11 2021
accepted: 08 02 2022
entrez: 17 11 2022
pubmed: 18 11 2022
medline: 22 11 2022
Statut: epublish

Résumé

Somatic hypermutation (SHM) is an important diversification mechanism that plays a part in the creation of immune memory. Immunoglobulin (Ig) variable region gene lineage trees were used over the last four decades to model SHM and the selection mechanisms operating on B cell clones. We hereby present IgTreeZ (Immunoglobulin Tree analyZer), a python-based tool that analyses many aspects of Ig gene lineage trees and their repertoires. Using simulations, we show that IgTreeZ can be reliably used for mutation and selection analyses. We used IgTreeZ on empirical data, found evidence for different mutation patterns in different B cell subpopulations, and gained insights into antigen-driven selection in corona virus disease 19 (COVID-19) patients. Most importantly, we show that including the CDR3 regions in selection analyses - which is only possible if these analyses are lineage tree-based - is crucial for obtaining correct results. Overall, we present a comprehensive lineage tree analysis tool that can reveal new biological insights into B cell repertoire dynamics.

Identifiants

pubmed: 36389731
doi: 10.3389/fimmu.2022.822834
pmc: PMC9643157
doi:

Substances chimiques

Immunoglobulin Variable Region 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

822834

Informations de copyright

Copyright © 2022 Neuman, Arrouasse, Kedmi, Cerutti, Magri and Mehr.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Références

Front Immunol. 2020 Aug 06;11:1734
pubmed: 32849618
Nucleic Acids Res. 2012 Sep 1;40(17):e134
pubmed: 22641856
Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W503-8
pubmed: 18503082
Bioinformatics. 2015 Oct 15;31(20):3356-8
pubmed: 26069265
Immunity. 2018 Oct 16;49(4):725-739.e6
pubmed: 30314758
Nucleic Acids Res. 2013 Jul;41(Web Server issue):W34-40
pubmed: 23671333
Nucleic Acids Res. 2005 Jan 1;33(Database issue):D256-61
pubmed: 15608191
Elife. 2021 Oct 18;10:
pubmed: 34661527
Cell. 2021 Feb 18;184(4):861-880
pubmed: 33497610
Clin Transl Immunology. 2021 Sep 05;10(9):e1339
pubmed: 34504693
Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22664-22672
pubmed: 31636219
J Theor Biol. 2008 Nov 21;255(2):210-22
pubmed: 18786548
JCI Insight. 2021 Feb 22;6(4):
pubmed: 33497357
Nat Immunol. 2015 Jul;16(7):755-65
pubmed: 26006014
Nat Biotechnol. 2017 Sep;35(9):879-884
pubmed: 28829438
J Mol Biol. 1982 May 5;157(1):105-32
pubmed: 7108955
Immunity. 2020 Dec 15;53(6):1136-1150
pubmed: 33326765
Eur J Immunol. 2008 Sep;38(9):2600-9
pubmed: 18792412
Bioinformatics. 2014 Jul 1;30(13):1930-2
pubmed: 24618469
Philos Trans R Soc Lond B Biol Sci. 2015 Sep 5;370(1676):
pubmed: 26194756
Nat Rev Immunol. 2015 Mar;15(3):137-48
pubmed: 25656706
Microbiol Spectr. 2014 Apr;2(2):
pubmed: 26105823
Int Immunol. 2010 Nov;22(11):875-87
pubmed: 21059768
Nat Rev Clin Oncol. 2019 Oct;16(10):634-652
pubmed: 31127191
J Immunol Methods. 2008 Sep 30;338(1-2):67-74
pubmed: 18706908
Sci Immunol. 2020 Jul 15;5(49):
pubmed: 32669287
Front Immunol. 2021 Jul 22;12:680687
pubmed: 34367141
Front Immunol. 2021 Mar 10;12:627813
pubmed: 33790900
Immunol Rev. 2018 Jul;284(1):24-41
pubmed: 29944754
J Immunol. 1999 Apr 1;162(7):3950-6
pubmed: 10201914
Cell Rep. 2021 May 25;35(8):109173
pubmed: 33991510
J Mol Recognit. 2004 Jan-Feb;17(1):17-32
pubmed: 14872534
Bioinformatics. 2017 Dec 15;33(24):3938-3946
pubmed: 28968873

Auteurs

Hadas Neuman (H)

The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.

Jessica Arrouasse (J)

The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.

Meirav Kedmi (M)

The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.
Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Ramat Gan, Israel.
Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel.

Andrea Cerutti (A)

Translational Clinical Research Program, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.
Catalan Institute for Research and Advanced Studies (ICREA), Barcelona, Spain.

Giuliana Magri (G)

Translational Clinical Research Program, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.

Ramit Mehr (R)

The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.

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