Protein-protein interaction (PPI) network and pathway enrichment analysis

First, 647 significantly upregulated genes were identified out of total 15,295 expressed genes through transcriptome analysis after 14 hours of CAD activation (Cutoff Log₂ fold change >0.6, P adj. value < 0.05). Then, functional interactions of these filtered genes were analyzed to extract underlying signaling pathways in the context of protein-protein interactions (PPIs). For that, STRING database (https://string-db.org) was used to generate a network of 936 interactions between 179 proteins, containing 37 additional interactomes. These functional interactions were extracted using STRING-resources (databases, networks, experiments, textmining, neighborhood, fusion, co-occurence and co-expression of interactomes). For functional and topological analysis of a PPI-network, cytoscape v3.8.2 software was used to identify hub proteins/core interactomes with higher degrees of interaction, fold increase and betweeness centrality within the network. Pathway enrichment analysis of these interactomes was performed using Metascape database (http://metascape.org) as previously described [32]. P value was adjusted to <0.05 to consider only statistically significant pathways. The information of significantly upregulated interferon-regulated genes (IRGs) in our gene expression datasets was extracted using all available resources (in vitro/in vivo data of Homo sapiens) on INTERFEROME v2.0 database [59]. While, innate immune response genes were identified through InnateDB curated genes database (https://www.innatedb.com) [60].