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

Hao Li; Qinglan Ma; Jingxin Ren; Wei Guo; Kaiyan Feng; Zhandong Li; Tao Huang; Yu-Dong Cai

doi:10.3389/fgene.2023.1157305

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

Front Genet. 2023 Mar 17:14:1157305. doi: 10.3389/fgene.2023.1157305. eCollection 2023.

Authors

Hao Li¹, Qinglan Ma², Jingxin Ren², Wei Guo³, Kaiyan Feng⁴, Zhandong Li¹, Tao Huang^{5

6}, Yu-Dong Cai²

Affiliations

¹ College of Food Engineering, Jilin Engineering Normal University, Changchun, China.
² School of Life Sciences, Shanghai University, Shanghai, China.
³ Key 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, China.
⁴ Department of Computer Science, Guangdong AIB Polytechnic College, Guangzhou, China.
⁵ Bio-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, China.
⁶ CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Abstract

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.

Keywords: COVID-19 vaccination; SARS-CoV-2 infection; classification rule; immune response; machine learning method.

Grants and funding

This research was funded by the National Key R&D Program of China [2022YFF1203202], Strategic Priority Research Program of Chinese Academy of Sciences [XDA26040304 and XDB38050200], the Fund of the Key Laboratory of Tissue Microenvironment and Tumor of Chinese Academy of Sciences [202002], Shandong Provincial Natural Science Foundation [ZR2022MC072].