Uncovering Transcriptional Dynamics in COVID-19: Integrating PBMC scRNA-Seq and RNA Velocity
Board Location: #173
Discipline: Computer Sciences and Information Management
Session: 1
Dania Zein - Tougaloo College
Co-Author(s): Xiuquan Wang, Tougaloo College, MS
Single-cell RNA sequencing (scRNA-seq) offers unparalleled resolution in profiling individual cells, enabling the identification of transcriptional changes and cellular characteristics associated with health and disease. This study applies scRNA-seq to peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and healthy controls to uncover immune dysregulation and identify potential therapeutic targets. We hypothesize that transcriptional changes in PBMCs reveal critical immune dysfunction linked to COVID-19 severity, offering insights that could guide therapeutic strategies. Using data from the GEO database (GSE149689), we analyzed 12,000 cells (1,500 per individual) from four COVID-19 patients and four healthy controls. A rigorous preprocessing pipeline—including mitochondrial and ribosomal gene filtering, doublet detection, and normalization—resulted in a refined dataset of 7,431 high-quality cells and 18,863 genes. Dimensionality reduction techniques, such as PCA, t-SNE, and UMAP, revealed distinct immune cell populations and transcriptional patterns associated with COVID-19. Differential gene expression analysis highlighted upregulated inflammatory pathways in monocytes and T-cell subtypes, shedding light on immune dysfunction in severe cases. To further enhance these findings, ongoing analyses will leverage RNA velocity for both cell type prediction and trajectory analysis. Cell type prediction will incorporate canonical immune cell markers alongside computational annotation tools, such as Velocyto and scVelo, to achieve precise classification of immune subtypes. By analyzing the dynamics of spliced and unspliced RNA reads, RNA velocity will map cellular transitions and predict future states, enabling the identification of critical lineage relationships, such as monocyte activation and T-cell exhaustion. These findings will provide a deeper understanding of immune cell dynamics during COVID-19 progression and inform strategies for mitigating immune dysregulation. Future efforts will validate these findings across diverse patient populations, explore real-time applicability, and extend the framework to other diseases, offering broader insights into immune-mediated pathologies.
Funder Acknowledgement(s): This research is supported by NSF HBCU UP Research Initiation Award (2300445), whose contributions have been invaluable in facilitating this work. The study aligns with institutional research goals and has received approval from faculty and the department.
Faculty Advisor: Xiuquan Wang, xwang@tougaloo.edu
Role: Data preprocessing