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Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data

Human immune systems are very complex, and the basis for individual differences in immune phenotypes is largely unclear. One reason is that the phenotype of the immune system is so complex that it is very difficult to describe its features and quantify differences between samples. To identify the ge...

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Autores principales: Okada, Daigo, Nakamura, Naotoshi, Setoh, Kazuya, Kawaguchi, Takahisa, Higasa, Koichiro, Tabara, Yasuharu, Matsuda, Fumihiko, Yamada, Ryo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144016/
https://www.ncbi.nlm.nih.gov/pubmed/33230199
http://dx.doi.org/10.1038/s10038-020-00874-x
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author Okada, Daigo
Nakamura, Naotoshi
Setoh, Kazuya
Kawaguchi, Takahisa
Higasa, Koichiro
Tabara, Yasuharu
Matsuda, Fumihiko
Yamada, Ryo
author_facet Okada, Daigo
Nakamura, Naotoshi
Setoh, Kazuya
Kawaguchi, Takahisa
Higasa, Koichiro
Tabara, Yasuharu
Matsuda, Fumihiko
Yamada, Ryo
author_sort Okada, Daigo
collection PubMed
description Human immune systems are very complex, and the basis for individual differences in immune phenotypes is largely unclear. One reason is that the phenotype of the immune system is so complex that it is very difficult to describe its features and quantify differences between samples. To identify the genetic factors that cause individual differences in whole lymphocyte profiles and their changes after vaccination without having to rely on biological assumptions, we performed a genome-wide association study (GWAS), using cytometry data. Here, we applied computational analysis to the cytometry data of 301 people before receiving an influenza vaccine, and 1, 7, and 90 days after the vaccination to extract the feature statistics of the lymphocyte profiles in a nonparametric and data-driven manner. We analyzed two types of cytometry data: measurements of six markers for B cell classification and seven markers for T cell classification. The coordinate values calculated by this method can be treated as feature statistics of the lymphocyte profile. Next, we examined the genetic basis of individual differences in human immune phenotypes with a GWAS for the feature statistics, and we newly identified seven significant and 36 suggestive single-nucleotide polymorphisms associated with the individual differences in lymphocyte profiles and their change after vaccination. This study provides a new workflow for performing combined analyses of cytometry data and other types of genomics data.
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spelling pubmed-81440162021-06-09 Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data Okada, Daigo Nakamura, Naotoshi Setoh, Kazuya Kawaguchi, Takahisa Higasa, Koichiro Tabara, Yasuharu Matsuda, Fumihiko Yamada, Ryo J Hum Genet Article Human immune systems are very complex, and the basis for individual differences in immune phenotypes is largely unclear. One reason is that the phenotype of the immune system is so complex that it is very difficult to describe its features and quantify differences between samples. To identify the genetic factors that cause individual differences in whole lymphocyte profiles and their changes after vaccination without having to rely on biological assumptions, we performed a genome-wide association study (GWAS), using cytometry data. Here, we applied computational analysis to the cytometry data of 301 people before receiving an influenza vaccine, and 1, 7, and 90 days after the vaccination to extract the feature statistics of the lymphocyte profiles in a nonparametric and data-driven manner. We analyzed two types of cytometry data: measurements of six markers for B cell classification and seven markers for T cell classification. The coordinate values calculated by this method can be treated as feature statistics of the lymphocyte profile. Next, we examined the genetic basis of individual differences in human immune phenotypes with a GWAS for the feature statistics, and we newly identified seven significant and 36 suggestive single-nucleotide polymorphisms associated with the individual differences in lymphocyte profiles and their change after vaccination. This study provides a new workflow for performing combined analyses of cytometry data and other types of genomics data. Springer Singapore 2020-11-23 2021 /pmc/articles/PMC8144016/ /pubmed/33230199 http://dx.doi.org/10.1038/s10038-020-00874-x Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Okada, Daigo
Nakamura, Naotoshi
Setoh, Kazuya
Kawaguchi, Takahisa
Higasa, Koichiro
Tabara, Yasuharu
Matsuda, Fumihiko
Yamada, Ryo
Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data
title Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data
title_full Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data
title_fullStr Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data
title_full_unstemmed Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data
title_short Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data
title_sort genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144016/
https://www.ncbi.nlm.nih.gov/pubmed/33230199
http://dx.doi.org/10.1038/s10038-020-00874-x
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