Immune responses of different COVID-19 vaccination strategies by analyzing single-cell RNA sequencing data from multiple tissues using machine learning methods

Multiple types of COVID-19 vaccines have been shown to be highly effective in preventing SARS-CoV-2 infection and in reducing post-infection symptoms. Almost all of these vaccines induce systemic immune responses, but differences in immune responses induced by different vaccination regimens are evid...

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Main Authors: Hao Li, Qinglan Ma, Jingxin Ren, Wei Guo, Kaiyan Feng, Zhandong Li, Tao Huang, Yu-Dong Cai
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2023.1157305/full
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author Hao Li
Qinglan Ma
Jingxin Ren
Wei Guo
Kaiyan Feng
Zhandong Li
Tao Huang
Tao Huang
Yu-Dong Cai
author_facet Hao Li
Qinglan Ma
Jingxin Ren
Wei Guo
Kaiyan Feng
Zhandong Li
Tao Huang
Tao Huang
Yu-Dong Cai
author_sort Hao Li
collection DOAJ
description Multiple types of COVID-19 vaccines have been shown to be highly effective in preventing SARS-CoV-2 infection and in reducing post-infection symptoms. Almost all of these vaccines induce systemic immune responses, but differences in immune responses induced by different vaccination regimens are evident. This study aimed to reveal the differences in immune gene expression levels of different target cells under different vaccine strategies after SARS-CoV-2 infection in hamsters. A machine learning based process was designed to analyze single-cell transcriptomic data of different cell types from the blood, lung, and nasal mucosa of hamsters infected with SARS-CoV-2, including B and T cells from the blood and nasal cavity, macrophages from the lung and nasal cavity, alveolar epithelial and lung endothelial cells. The cohort was divided into five groups: non-vaccinated (control), 2*adenovirus (two doses of adenovirus vaccine), 2*attenuated (two doses of attenuated virus vaccine), 2*mRNA (two doses of mRNA vaccine), and mRNA/attenuated (primed by mRNA vaccine, boosted by attenuated vaccine). All genes were ranked using five signature ranking methods (LASSO, LightGBM, Monte Carlo feature selection, mRMR, and permutation feature importance). Some key genes that contributed to the analysis of immune changes, such as RPS23, DDX5, PFN1 in immune cells, and IRF9 and MX1 in tissue cells, were screened. Afterward, the five feature sorting lists were fed into the feature incremental selection framework, which contained two classification algorithms (decision tree [DT] and random forest [RF]), to construct optimal classifiers and generate quantitative rules. Results showed that random forest classifiers could provide relative higher performance than decision tree classifiers, whereas the DT classifiers provided quantitative rules that indicated special gene expression levels under different vaccine strategies. These findings may help us to develop better protective vaccination programs and new vaccines.
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spelling doaj.art-f2c22b3431f744f2a1cb8492245772912023-03-17T04:29:38ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-03-011410.3389/fgene.2023.11573051157305Immune responses of different COVID-19 vaccination strategies by analyzing single-cell RNA sequencing data from multiple tissues using machine learning methodsHao Li0Qinglan Ma1Jingxin Ren2Wei Guo3Kaiyan Feng4Zhandong Li5Tao Huang6Tao Huang7Yu-Dong Cai8College of Food Engineering, Jilin Engineering Normal University, Changchun, ChinaSchool of Life Sciences, Shanghai University, Shanghai, ChinaSchool of Life Sciences, Shanghai University, Shanghai, ChinaKey Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences (SIBS), Shanghai Jiao Tong University School of Medicine (SJTUSM), Chinese Academy of Sciences (CAS), Shanghai, ChinaDepartment of Computer Science, Guangdong AIB Polytechnic College, Guangzhou, ChinaCollege of Food Engineering, Jilin Engineering Normal University, Changchun, ChinaBio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaSchool of Life Sciences, Shanghai University, Shanghai, ChinaMultiple types of COVID-19 vaccines have been shown to be highly effective in preventing SARS-CoV-2 infection and in reducing post-infection symptoms. Almost all of these vaccines induce systemic immune responses, but differences in immune responses induced by different vaccination regimens are evident. This study aimed to reveal the differences in immune gene expression levels of different target cells under different vaccine strategies after SARS-CoV-2 infection in hamsters. A machine learning based process was designed to analyze single-cell transcriptomic data of different cell types from the blood, lung, and nasal mucosa of hamsters infected with SARS-CoV-2, including B and T cells from the blood and nasal cavity, macrophages from the lung and nasal cavity, alveolar epithelial and lung endothelial cells. The cohort was divided into five groups: non-vaccinated (control), 2*adenovirus (two doses of adenovirus vaccine), 2*attenuated (two doses of attenuated virus vaccine), 2*mRNA (two doses of mRNA vaccine), and mRNA/attenuated (primed by mRNA vaccine, boosted by attenuated vaccine). All genes were ranked using five signature ranking methods (LASSO, LightGBM, Monte Carlo feature selection, mRMR, and permutation feature importance). Some key genes that contributed to the analysis of immune changes, such as RPS23, DDX5, PFN1 in immune cells, and IRF9 and MX1 in tissue cells, were screened. Afterward, the five feature sorting lists were fed into the feature incremental selection framework, which contained two classification algorithms (decision tree [DT] and random forest [RF]), to construct optimal classifiers and generate quantitative rules. Results showed that random forest classifiers could provide relative higher performance than decision tree classifiers, whereas the DT classifiers provided quantitative rules that indicated special gene expression levels under different vaccine strategies. These findings may help us to develop better protective vaccination programs and new vaccines.https://www.frontiersin.org/articles/10.3389/fgene.2023.1157305/fullimmune responseCOVID-19 vaccinationSARS-CoV-2 infectionmachine learning methodclassification rule
spellingShingle Hao Li
Qinglan Ma
Jingxin Ren
Wei Guo
Kaiyan Feng
Zhandong Li
Tao Huang
Tao Huang
Yu-Dong Cai
Immune responses of different COVID-19 vaccination strategies by analyzing single-cell RNA sequencing data from multiple tissues using machine learning methods
Frontiers in Genetics
immune response
COVID-19 vaccination
SARS-CoV-2 infection
machine learning method
classification rule
title Immune responses of different COVID-19 vaccination strategies by analyzing single-cell RNA sequencing data from multiple tissues using machine learning methods
title_full Immune responses of different COVID-19 vaccination strategies by analyzing single-cell RNA sequencing data from multiple tissues using machine learning methods
title_fullStr Immune responses of different COVID-19 vaccination strategies by analyzing single-cell RNA sequencing data from multiple tissues using machine learning methods
title_full_unstemmed Immune responses of different COVID-19 vaccination strategies by analyzing single-cell RNA sequencing data from multiple tissues using machine learning methods
title_short Immune responses of different COVID-19 vaccination strategies by analyzing single-cell RNA sequencing data from multiple tissues using machine learning methods
title_sort immune responses of different covid 19 vaccination strategies by analyzing single cell rna sequencing data from multiple tissues using machine learning methods
topic immune response
COVID-19 vaccination
SARS-CoV-2 infection
machine learning method
classification rule
url https://www.frontiersin.org/articles/10.3389/fgene.2023.1157305/full
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