Fig. 3: Transcriptional landscape of the NIBIT-M4 trial.

a Gene Set Enrichment Analysis (GSEA, as implemented in clusterProfiler⁸⁴) from supervised differential analysis between R (n = 6) and NR (n = 8) patients (negative binomial generalized linear model with likelihood ratio test (glmLRT), as implemented in EdgeR⁸²) before treatment (week 0) and after four (week 4) and twelve (week 12) weeks. x axis reports the aggregated p value of significant enriched GO:BP terms (false discovery rate method from empirical permutation test, FDR < 0.1), computed using Fisher method and classified into seven main categories. Size of the dot represents the number of GO:BP terms grouped into a category; color of the dots represents the mean Normalized Enrichment Score (NES) of the terms. b Volcano plot (left) of differentially expressed genes (p value < 0.05 from glmLRT, as implemented in EdgeR⁸²) between R (n = 6) and NR (n = 8) patients, labeled genes belong to the guadecitabine-specific gene signature¹⁰. x axis reports the effect size (in log scale), y axis reports the −log(p value) from glmLRT, as implemented in EdgeR⁸². GSEA enrichment (right) of the guadecitabine-specific signature on the ranked list of differentially expressed gene at week 4 and week 12. c Same as in b using the dataset from a trial of combined therapy ICI plus HMA from Chen et al. 2022¹⁴ (C2D8 post-treatment, n = 4 R and n = 5 NR). Source data are provided as a Source Data file.