Transcriptomic and miRNA Signatures of ChAdOx1 nCoV-19 Vaccine Response Using Machine Learning

Abstract

Vaccination with ChAdOx1 nCoV-19 is an important countermeasure to fight the COVID-19 pandemic. This vaccine enhances human immunoprotection against SARS-CoV-2 by inducing an immune response against the SARS-CoV-2 S protein. However, the immune-related genes induced by vaccination remain to be identified. This study employs feature ranking algorithms, an incremental feature selection method, and classification algorithms to analyze transcriptomic data from an experimental group vaccinated with the ChAdOx1 nCoV-19 vaccine and a control group vaccinated with the MenACWY meningococcal vaccine. According to different time points, vaccination status, and SARS-CoV-2 infection status, the transcriptomic data was divided into five groups, including a pre-vaccination group, ChAdOx1-onset group, MenACWY-onset group, ChAdOx1-7D group, and MenACWY-7D group. Each group contained samples with 13,383 RNA features and 1662 small RNA features. The results identified key genes that could indicate the efficacy of the ChAdOx1 nCoV-19 vaccine, and a classifier was developed to classify samples into the above groups. Additionally, effective classification rules were established to distinguish between different vaccination statuses. It was found that subjects vaccinated with ChAdOx1 nCoV-19 vaccine and infected with SARS-CoV-2 were characterized by up-regulation of HIST1H3G expression and down-regulation of CASP10 expression. In addition, IGHG1, FOXM1, and CASP10 genes were strongly associated with ChAdOx1 nCoV-19 vaccine efficacy. Compared with previous omics-driven studies, the machine learning algorithms used in this study were able to analyze transcriptome data faster and more comprehensively to identify potential markers associated with vaccine effect and investigate ChAdOx1 nCoV-19 vaccine-induced gene expression changes. These observations contribute to an understanding of the immune protection and inflammatory responses induced by the ChAdOx1 nCoV-19 vaccine during symptomatic episodes and provide a rationale for improving vaccine efficacy.

Keywords

• ChAdOx1 nCoV-19 vaccination
• gene signature
• miRNA signature
• machine learning