3.5 Identification of key hubs
We identified 291 key hubs using the causal reasoning method which seeks to identify molecular regulators that will directly cause the observed transcriptional changes in response to BCG vaccination. Key regulators can be transcriptional factors and proteins with potentially altered activity that explains the transcriptional changes. Top five statistically significant inhibited key hubs were: HEY1, DSIPI (GILZ), Jagged1, HAND1 and miR-129-1-3p. And top five statistically significant activated key hubs were: PHF20, TAFII70, Glutaredoxin, RUNX2 and NOTCH1 (NICD). Top 30 causal key hubs are shown in table 1 and all identified 291 key hubs are included in table S4 (Supporting Information).