3.4 BCG protein-protein interactions (PPIs)
All 22 genes in BCG-CGS were used as seed nodes to build a protein-protein interaction network for signature genes (Figure 2B). Interactions were extracted from STRING database and included high confidence interactions including: physical interactions (e.g., binding), functional interactions (e.g., activation, inhibition, catalysis), or gene co-expression. Two types of networks were generated: 1) high-confidence ‘core’ network restricted to BCG signature genes as network nodes and high confidence (\(\geq 0.70)\ \)interactions as network edges, and 2) medium-confidence interaction network obtained from expanding the core network by 20 additional nodes (Figure 3).
Enrichment analysis results performed in Cytoscape, using STRING’s protein-protein interactions, indicated that BCG-CGS is enriched in inflammatory cytokines and immune response modulators (Figure 2B). Some signature genes are also involved in the negative control of important viral processes (e.g., (FCN1, TNF and CCL3), and others are involved in the response to viral infections (e.g., IFNG, RNASE6, IL6 and TNF). The complete lists of enriched pathways are included in tables S2 and S3 (Supporting Information).