Discovery of Drug-Responsive Phenomic Alteration-Related Driver Genes in the Treatment of Coronary Heart Disease

Background: The Xueyu Zheng (XYZ) phenome is central to coronary heart disease (CHD), but efforts to detect genetic associations in the XYZ phenome have been disappointing. Methods: The phenomic alteration-related genes (PARGs) for the XYZ phenome were screened using |rho| > 0.4 and p < 0.05 after treatment with Danhong injection at day 14 and day 30. Then, the driver genes for the Protein-Protein Interaction (PPI) networks of the PARGs established using STRING 11.0 were detected using a personalized network control algorithm (PNC). Finally, the molecular correlations of the driver genes with the XYZ phenome were analyzed with the Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways from a holistic viewpoint. Results: A total of 525 and 309 PARGs in the XYZ phenome at day 14 and day 30 were identified. These genes were separately enriched in 48 and 35 pathways. Furthermore, five driver genes were detected. These genes were mainly correlated with endoplasmic reticulum stress-mediated apoptosis and autophagy regulation, which could suppress atherosclerosis progression. Conclusion: Our study detected the drug-responsive PARGs of the XYZ phenome in CHD and provides an exemplary strategy to investigate the genetic associations among this common phenome and its component symptoms in patients with CHD. Trial Registration: ClinicalTrials.gov, NCT01681316; registered on September 7, 2012.