Fig. 4: Hallmark pathway gene set enrichment analysis and gene expression comparison in HRZE and NTZ treated arms.

A Hallmark gene pathway changes associated with 2 weeks of HRZE (A) or NTZ (B). Positive are pathways overrepresented at 2 weeks of therapy (up), and negative are pathways underrepresented at 2 weeks (down), both compared to baseline. All pathways are significant (FDR < 0.05, see Supplementary Data 6) with the size of the arrow indicating level of significance. Only pathways from MiSigDB Hallmark pathway set found to be significantly altered in this analysis are shown. Here NES stands for Normalized Enrichment Score. B, C TB-associated peripheral blood transcripts from ref. ¹⁹, highlighting post treatment vs baseline changes in gene expression for HRZE (B) or NTZ (C). Notably, HRZE renormalizes (i.e., towards a healthy control state) the expression of 144 validated TB inflammatory transcripts and exacerbates only 13 (see Supplementary Data 7). NTZ is found only to exacerbate four (see Supplementary Data 8). TB-associated peripheral blood transcripts significantly affected by each treatment were those determined to have a Benjamini–Hochberg false discovery rate (FDR) adjusted p-value less than 0.05 for the variable Group in the limma/voom model (see “Methods” section). D, E Effect of HRZE and NTZ on blood gene expression for a set of IBD-associated genes from Palmer, et al.⁴¹. Both HRZE (D) and NTZ (E) cause different genes to either renormalize (HRZE 66, NTZ 34) (see Supplementary Data 9) or exacerbate (HRZE 55, NTZ 21) (see Supplementary Data 10). IBD-associated peripheral blood transcripts significantly affected by each treatment were those determined to have a Benjamini–Hochberg false discovery rate (FDR) adjusted p-value less than 0.05 for the variable Group in the limma/voom model (see “Methods” section) P value in y axis is adjusted according to Benjamini–Hochberg (FDR). Source data are provided as a Source Data file.