IgIDivA : immunoglobulin intraclonal diversification analysis
Zaragoza-Infante, Laura (Aristotle University of Thessalonik)
Junet, Valentin (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Pechlivanis, Nikos (Centre for Research and Technology Hellas (Tessalònica, Grècia))
Fragkouli, Styliani-Christina (Centre for Research and Technology Hellas (Tessalònica, Grècia))
Amprachamian, Serovpe (Centre for Research and Technology Hellas (Tessalònica, Grècia))
Koletsa, Triantafyllia (Aristotle University of Thessaloniki)
Chatzidimitriou, Anastasia (Centre for Research and Technology Hellas (Tessalònica, Grècia))
Papaioannou, Maria (Aristotle University of Thessaloniki)
Stamatopoulos, Kostas (Centre for Research and Technology Hellas (Tessalònica, Grècia))
Agathangelidis, Andreas (University of Athens)
Psomopoulos, Fotis (Centre for Research and Technology Hellas (Tessalònica, Grècia))

Date:	2022
Abstract:	Intraclonal diversification (ID) within the immunoglobulin (IG) genes expressed by B cell clones arises due to ongoing somatic hypermutation (SHM) in a context of continuous interactions with antigen(s). Defining the nature and order of appearance of SHMs in the IG genes can assist in improved understanding of the ID process, shedding light into the ontogeny and evolution of B cell clones in health and disease. Such endeavor is empowered thanks to the introduction of high-throughput sequencing in the study of IG gene repertoires. However, few existing tools allow the identification, quantification and characterization of SHMs related to ID, all of which have limitations in their analysis, highlighting the need for developing a purpose-built tool for the comprehensive analysis of the ID process. In this work, we present the immunoglobulin intraclonal diversification analysis (IgIDivA) tool, a novel methodology for the in-depth qualitative and quantitative analysis of the ID process from high-throughput sequencing data. IgIDivA identifies and characterizes SHMs that occur within the variable domain of the rearranged IG genes and studies in detail the connections between identified SHMs, establishing mutational pathways. Moreover, it combines established and new graph-based metrics for the objective determination of ID level, combined with statistical analysis for the comparison of ID level features for different groups of samples. Of importance, IgIDivA also provides detailed visualizations of ID through the generation of purpose-built graph networks. Beyond the method design, IgIDivA has been also implemented as an R Shiny web application. IgIDivA is freely available at https://bio. tools/igidiva.
Grants:	European Commission 765158
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Intraclonal diversification ; B cell receptor immunoglobulin ; High-throughput sequencing ; Graph networks ; Graph metrics
Published in:	Briefings in Bioinformatics, Vol. 23, Issue 5 (September 2022) , art. bbac349, ISSN 1477-4054

DOI: 10.1093/bib/bbac349
PMID: 36044248

11 p, 1.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles