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Tracing the evolutionary pathway of SARS-CoV-2 through RNA sequencing analysis
Mostafa Rezapour1, Sean V Murphy2, David A Ornelles3
1Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA. mrezapou@wakehealth.edu.
Scientific Reports
|July 4, 2025
Summary
This study analyzed gene expression in COVID-19 variants using RNA sequencing. Transcriptomic signatures accurately detect SARS-CoV-2 infection across variants, aiding diagnostics and therapeutics.
Area of Science:
- Genomics
- Virology
- Immunology
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, necessitates understanding viral evolution and host responses.
- RNA sequencing (RNA-Seq) is crucial for analyzing gene expression changes during infection.
Purpose of the Study:
- To analyze gene expression differences across SARS-CoV-2 variants using RNA-Seq.
- To identify variant-agnostic transcriptomic signatures for COVID-19 detection.
- To assess the evolutionary impact of SARS-CoV-2 variants on host pathways.
Main Methods:
- Utilized publicly available RNA-Seq datasets (GEO IDs: GSE157103, GSE171110, GSE189039, GSE201530).
- Employed Generalized Linear Models with Quasi-Likelihood F-tests and Magnitude-Altitude Scoring (GLMQL-MAS) for gene expression analysis.
- Conducted Gene Ontology (GO) and pathway analyses, followed by Cross-MAS for signature identification and classification.
Main Results:
- Early SARS-CoV-2 variants (Wuhan, French) impacted viral replication pathways.
- Later variants (Beta, Omicron) modulated host immune response pathways (e.g., Interferon, Cytokine signaling).
- Identified key genes (IFI27, CDC20, RRM2, HJURP, CDC45) achieving up to 97.31% accuracy in classifying COVID-19 across datasets.
Conclusions:
- SARS-CoV-2 variants exhibit an evolutionary shift in host interaction, from replication to immune evasion.
- Transcriptomic signatures offer a robust, variant-agnostic approach for COVID-19 detection.
- Findings support flexible diagnostic and therapeutic strategies against evolving SARS-CoV-2 strains.
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