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DSab-origin: a novel IGHD sensitive VDJ mapping method and its application on antibody response after influenza vaccination

BACKGROUND: Functional antibody genes are often assembled by VDJ recombination and then diversified by somatic hypermutation. Identifying the combination of sourcing germline genes is critical to understand the process of antibody maturation, which may facilitate the diagnostics and rapid generation...

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Autores principales: Zhang, Qingchen, Zhang, Lu, Zhou, Chen, Yang, Yiyan, Yin, Zuojing, Wu, Dingfeng, Tang, Kailin, Cao, Zhiwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417009/
https://www.ncbi.nlm.nih.gov/pubmed/30871465
http://dx.doi.org/10.1186/s12859-019-2715-7
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author Zhang, Qingchen
Zhang, Lu
Zhou, Chen
Yang, Yiyan
Yin, Zuojing
Wu, Dingfeng
Tang, Kailin
Cao, Zhiwei
author_facet Zhang, Qingchen
Zhang, Lu
Zhou, Chen
Yang, Yiyan
Yin, Zuojing
Wu, Dingfeng
Tang, Kailin
Cao, Zhiwei
author_sort Zhang, Qingchen
collection PubMed
description BACKGROUND: Functional antibody genes are often assembled by VDJ recombination and then diversified by somatic hypermutation. Identifying the combination of sourcing germline genes is critical to understand the process of antibody maturation, which may facilitate the diagnostics and rapid generation of human monoclonal antibodies in therapeutics. Despite of successful efforts in V and J fragment assignment, method in D segment tracing remains weak for immunoglobulin heavy diversity (IGHD). RESULTS: In this paper, we presented a D-sensitive mapping method called DSab-origin with accuracies around 90% in human monoclonal antibody data and average 95.8% in mouse data. Besides, DSab-origin achieved the best performance in holistic prediction of VDJ segments assignment comparing with other methods commonly used in simulation data. After that, an application example was explored on the antibody response based on a time-series antibody sequencing data after influenza vaccination. The result indicated that, despite the personal response among different donors, IGHV3–7 and IGHD4–17 were likely to be dominated gene segments in these three donors. CONCLUSIONS: This work filled in a computational gap in D segment assignment for VDJ germline gene identification in antibody research. And it offered an application example of DSab-origin for studying the antibody maturation process after influenza vaccination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2715-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-64170092019-03-25 DSab-origin: a novel IGHD sensitive VDJ mapping method and its application on antibody response after influenza vaccination Zhang, Qingchen Zhang, Lu Zhou, Chen Yang, Yiyan Yin, Zuojing Wu, Dingfeng Tang, Kailin Cao, Zhiwei BMC Bioinformatics Methodology Article BACKGROUND: Functional antibody genes are often assembled by VDJ recombination and then diversified by somatic hypermutation. Identifying the combination of sourcing germline genes is critical to understand the process of antibody maturation, which may facilitate the diagnostics and rapid generation of human monoclonal antibodies in therapeutics. Despite of successful efforts in V and J fragment assignment, method in D segment tracing remains weak for immunoglobulin heavy diversity (IGHD). RESULTS: In this paper, we presented a D-sensitive mapping method called DSab-origin with accuracies around 90% in human monoclonal antibody data and average 95.8% in mouse data. Besides, DSab-origin achieved the best performance in holistic prediction of VDJ segments assignment comparing with other methods commonly used in simulation data. After that, an application example was explored on the antibody response based on a time-series antibody sequencing data after influenza vaccination. The result indicated that, despite the personal response among different donors, IGHV3–7 and IGHD4–17 were likely to be dominated gene segments in these three donors. CONCLUSIONS: This work filled in a computational gap in D segment assignment for VDJ germline gene identification in antibody research. And it offered an application example of DSab-origin for studying the antibody maturation process after influenza vaccination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2715-7) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-14 /pmc/articles/PMC6417009/ /pubmed/30871465 http://dx.doi.org/10.1186/s12859-019-2715-7 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Methodology Article
Zhang, Qingchen
Zhang, Lu
Zhou, Chen
Yang, Yiyan
Yin, Zuojing
Wu, Dingfeng
Tang, Kailin
Cao, Zhiwei
DSab-origin: a novel IGHD sensitive VDJ mapping method and its application on antibody response after influenza vaccination
title DSab-origin: a novel IGHD sensitive VDJ mapping method and its application on antibody response after influenza vaccination
title_full DSab-origin: a novel IGHD sensitive VDJ mapping method and its application on antibody response after influenza vaccination
title_fullStr DSab-origin: a novel IGHD sensitive VDJ mapping method and its application on antibody response after influenza vaccination
title_full_unstemmed DSab-origin: a novel IGHD sensitive VDJ mapping method and its application on antibody response after influenza vaccination
title_short DSab-origin: a novel IGHD sensitive VDJ mapping method and its application on antibody response after influenza vaccination
title_sort dsab-origin: a novel ighd sensitive vdj mapping method and its application on antibody response after influenza vaccination
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417009/
https://www.ncbi.nlm.nih.gov/pubmed/30871465
http://dx.doi.org/10.1186/s12859-019-2715-7
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