Characterization of Chronic Lymphocytic Leukemia Immunoglobulin Rearrangements from Partial Read Sequencing

The determination of the mutational status in the immunoglobulin variable region is an established prognostic biomarker for chronic lymphocytic leukemia (CLL). The length and inner variability of the variable, diversity, and joining (VDJ) rearranged sequences compromise B-cell clone characterization...

Descripción completa

Detalles Bibliográficos
Autores: Fuentes-Trillo A, Serrano-Alcalá A, Ferrer-Lores B, Ventura-López L, Seda E, García-García AB, Navarro B, Terol MJ, Chaves FJ
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p20023
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/20023
Access Level:acceso abierto
Palabra clave:Chronic lymphocytic leukemia
IGH locus
NGS
B cell
Immune repertoire
id ES_13a89fcee3cd179434af2affc7b71067
oai_identifier_str oai:incliva.fundanetsuite.com:p20023
network_acronym_str ES
network_name_str España
repository_id_str
spelling Characterization of Chronic Lymphocytic Leukemia Immunoglobulin Rearrangements from Partial Read SequencingFuentes-Trillo ASerrano-Alcalá AFerrer-Lores BVentura-López LSeda EGarcía-García ABNavarro BTerol MJChaves FJChronic lymphocytic leukemiaIGH locusNGSB cellImmune repertoireThe determination of the mutational status in the immunoglobulin variable region is an established prognostic biomarker for chronic lymphocytic leukemia (CLL). The length and inner variability of the variable, diversity, and joining (VDJ) rearranged sequences compromise B-cell clone characterization using next-generation sequencing (NGS), and a standardization is needed to adapt the procedure to the current clinical guidelines. Here, we develop a complete strategy for sequencing the variable domain of the immunoglobulin heavy chain (IGH) locus with a simple, low-cost, and efficient method that enables sequencing using shorter reads (MiSeq 150 x 2), allowing for faster results. Clonality and mutational status determination are performed within the same analysis pipeline. We tested and validated the method using 319 CLL patients previously diagnosed with IGH locus characterized using Sanger sequencing, along with 47 healthy donor samples. The analysis method follows a clone-centered consensus sequence strategy to identify B-cell clones and establish a clonal threshold specific for each patient's clonality profile, thereby overcoming the limitations of Sanger sequencing which is the gold standard used for determining immunoglobulin heavy variable (IGHV) mutational status.OXFORD UNIV PRESS2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/20023GENOMICS PROTEOMICS & BIOINFORMATICSISSN: 16720229ISSNe: 22103244reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p200232026-06-07T16:35:31Z
dc.title.none.fl_str_mv Characterization of Chronic Lymphocytic Leukemia Immunoglobulin Rearrangements from Partial Read Sequencing
title Characterization of Chronic Lymphocytic Leukemia Immunoglobulin Rearrangements from Partial Read Sequencing
spellingShingle Characterization of Chronic Lymphocytic Leukemia Immunoglobulin Rearrangements from Partial Read Sequencing
Fuentes-Trillo A
Chronic lymphocytic leukemia
IGH locus
NGS
B cell
Immune repertoire
title_short Characterization of Chronic Lymphocytic Leukemia Immunoglobulin Rearrangements from Partial Read Sequencing
title_full Characterization of Chronic Lymphocytic Leukemia Immunoglobulin Rearrangements from Partial Read Sequencing
title_fullStr Characterization of Chronic Lymphocytic Leukemia Immunoglobulin Rearrangements from Partial Read Sequencing
title_full_unstemmed Characterization of Chronic Lymphocytic Leukemia Immunoglobulin Rearrangements from Partial Read Sequencing
title_sort Characterization of Chronic Lymphocytic Leukemia Immunoglobulin Rearrangements from Partial Read Sequencing
dc.creator.none.fl_str_mv Fuentes-Trillo A
Serrano-Alcalá A
Ferrer-Lores B
Ventura-López L
Seda E
García-García AB
Navarro B
Terol MJ
Chaves FJ
author Fuentes-Trillo A
author_facet Fuentes-Trillo A
Serrano-Alcalá A
Ferrer-Lores B
Ventura-López L
Seda E
García-García AB
Navarro B
Terol MJ
Chaves FJ
author_role author
author2 Serrano-Alcalá A
Ferrer-Lores B
Ventura-López L
Seda E
García-García AB
Navarro B
Terol MJ
Chaves FJ
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Chronic lymphocytic leukemia
IGH locus
NGS
B cell
Immune repertoire
topic Chronic lymphocytic leukemia
IGH locus
NGS
B cell
Immune repertoire
description The determination of the mutational status in the immunoglobulin variable region is an established prognostic biomarker for chronic lymphocytic leukemia (CLL). The length and inner variability of the variable, diversity, and joining (VDJ) rearranged sequences compromise B-cell clone characterization using next-generation sequencing (NGS), and a standardization is needed to adapt the procedure to the current clinical guidelines. Here, we develop a complete strategy for sequencing the variable domain of the immunoglobulin heavy chain (IGH) locus with a simple, low-cost, and efficient method that enables sequencing using shorter reads (MiSeq 150 x 2), allowing for faster results. Clonality and mutational status determination are performed within the same analysis pipeline. We tested and validated the method using 319 CLL patients previously diagnosed with IGH locus characterized using Sanger sequencing, along with 47 healthy donor samples. The analysis method follows a clone-centered consensus sequence strategy to identify B-cell clones and establish a clonal threshold specific for each patient's clonality profile, thereby overcoming the limitations of Sanger sequencing which is the gold standard used for determining immunoglobulin heavy variable (IGHV) mutational status.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/20023
url https://incliva.portalinvestigacion.com/publicaciones/20023
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv OXFORD UNIV PRESS
publisher.none.fl_str_mv OXFORD UNIV PRESS
dc.source.none.fl_str_mv GENOMICS PROTEOMICS & BIOINFORMATICS
ISSN: 16720229
ISSNe: 22103244
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869403689124364288
score 15,812455

Similares en LA Referencia