Fig. 2
Integrative genome-wide transcriptomic and epigenomic analysis identifies candidate molecular pathways of chemotherapy response. a Schematic representation of the integrative transcriptomic and epigenomic analysis: first, patients are defined by their response to chemotherapy; second, our method integrates patients’ transcriptomic and epigenomic profiles; third, candidate pathways affected on both transcriptomic and epigenomic levels are identified; and finally, our method employs multi-modal validation of candidate pathways. b Box and whisker plot depicting p-value cutoff for query carboplatin–paclitaxel response composite methylation pathway signature (x-axis) and NESs from the corresponding GSEA comparison between composite methylation and expression pathways signatures (y-axis), based on analysis in TCGA-LUAD patient cohort. Arrow indicated optimal p-value threshold, which results in the strongest GSEA enrichment. c GSEA comparing carboplatin–paclitaxel response composite expression pathway signature (reference) and carboplatin–paclitaxel response composite methylation pathway signature (query, NES p ≤ 0.001), based on analysis in TCGA-LUAD patient cohort. Horizontal red bar indicates leading edge pathways altered on both transcriptomic and epigenomic levels. NES and p-value were estimated using 1000 pathway permutations. d ROC analysis comparing ability of the 7 candidate pathways to predict carboplatin–paclitaxel where their activity is defined based on their expression values (green) or methylation values (blue). AUROC is indicated
