IgTreeZ, A toolkit for immunoglobulin gene lineage tree-based analysis, reveals CDR3s are crucial for selection analysis

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  • dc.contributor.author Neuman, Hadas
  • dc.contributor.author Arrouasse, Jessica
  • dc.contributor.author Kedmi, Meirav
  • dc.contributor.author Cerutti, Andrea, 1965-
  • dc.contributor.author Magri, Giuliana, 1978-
  • dc.contributor.author Mehr, Ramit
  • dc.date.accessioned 2023-04-04T06:02:26Z
  • dc.date.available 2023-04-04T06:02:26Z
  • dc.date.issued 2022
  • dc.description.abstract 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.
  • dc.description.sponsorship HN was supported by a Bar-Ilan University President’s Scholarship. AC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) grant RTI2018-093894-B-100. GM is supported by Spanish Institute of Health Carlos III (Miguel Servet grant 2020-2024).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Neuman H, Arrouasse J, Kedmi M, Cerutti A, Magri G, Mehr R. IgTreeZ, A toolkit for immunoglobulin gene lineage tree-based analysis, reveals CDR3s are crucial for selection analysis. Front Immunol. 2022 Oct 26;13:822834. DOI: 10.3389/fimmu.2022.822834
  • dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2022.822834
  • dc.identifier.issn 1664-3224
  • dc.identifier.uri http://hdl.handle.net/10230/56403
  • dc.language.iso eng
  • dc.publisher Frontiers
  • dc.relation.ispartof Front Immunol. 2022 Oct 26;13:822834
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-093894-B-100
  • dc.rights © 2022 Neuman, Arrouasse, Kedmi, Cerutti, Magri and Mehr. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword B cell receptor (BCR)
  • dc.subject.keyword B cell repertoire
  • dc.subject.keyword Antibody
  • dc.subject.keyword Immunoglobulin
  • dc.subject.keyword Lineage tree
  • dc.subject.keyword Somatic hypermutation (SHM)
  • dc.title IgTreeZ, A toolkit for immunoglobulin gene lineage tree-based analysis, reveals CDR3s are crucial for selection analysis
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion