Single-Cell RNA Sequencing to Identify Natural Killer Cell-Linked Genetic Markers and Regulatory Biomolecules in Coronary Heart Disease

Objectives: Infections with bacteria and viruses have been linked to an increase in the risk of Coronary Heart Disease (CHD). The development of CHD may be influenced by Natural Killer cells (NK), which are the first defense system of the body in opposition to these infections. This study aimed to compare scRNA-seq and transcriptomics data to find natural killer cell-linked genetic biomarkers that might potentially be used for the diagnosis and assessment of CHD. Methods: Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing datasets were analyzed to bring out Differentially Expressed Genes (DEGs). To ascertain the function of these DEGs, we used gene set enrichment analysis with Gene Ontology (GO) and metabolic pathways using FunRich, DAVID, and SRplot tools. Hub proteins were identified from Protein-Protein Interaction (PPI) network analysis and also discovered transcription factors, post-transcription factors, and chemical compounds. Biomarker validation of CHD was carried out via probability analysis through the Receiver Operating Characteristic (ROC) curve. Results: A total of 106 shared DEGs were identified after integrating genes and cross-comparative analysis. Signal transduction, cell-to-cell communication, immune activation, immune responses, cytoplasm pathway, plasma membrane, transcription factor, MHC class II, and receptor activity are the most enrichment GO term, while cell adhesion molecules, immune system, TYROBP, LCK, FYN, and T-cell receptor signaling pathways are key metabolic pathways. An interconnected system of Protein- Protein Interactions (PPI) identified the top hub proteins, including CDK1 and PTPRC, which could serve as potential biomarkers through network topology analysis. Furthermore, several transcription factors (YY1, PPARG, NFIC, FOXC1, GATA2, NFKB1, RELA and TP53) and translation factors (hsa-mir-195-5p, hsa-mir-34a-5p, hsa-mir-16-5p and hsa-mir-124-3p) were discovered in this investigation. It was also anticipated that some drug-like compounds might be advantageous against CHD. Conclusion: To have a deeper understanding of molecular pathways and to create effective treatments for CHD, this study provides molecularly predicted biomarkers at the gene expression level and protein basis.