Fig. 4: Transcriptomic alterations and signaling pathway dynamics in drug-naïve and resistant HGSOC models.

a Schematic overview of the experimental workflow for generating long-term (lt-res), intermediate (i-res), and short-term (st-res) drug-resistant models. b UMAP plots showing the distribution of drug-naïve and resistant cells for each HGSOC cell line. Colors denote cell line and treatment condition. c Energy-distance (E-distance) heatmaps illustrating the degree of transcriptomic perturbation in parental, ADA- and PTX- resistant cells. Color intensity reflects the degree of perturbation, with darker shades indicating higher perturbation and lighter shades indicating lower perturbation. Color annotations correspond to identities as shown in panel b. d Heatmaps illustrating the scaled signaling pathway activity scores of PROGENy pathways in PTX-res and ADA-res cell lines and the parental cells. Red color indicates higher pathway activity scores, and blue color indicates lower pathway activity scores. e Enrichment analysis by Fisher’s exact test of differentially expressed genes (logFC ≥ |0.5 | , adjusted p-value ≤ 0.1) in all ADA st-res and PTX st-res cells, compared to drug-naive cells. The top 10 most significantly enriched pathways were reported for both upregulated and downregulated genes in st-res cells, from REACTOME, MSigDB HALLMARKS, PID, and KEGG terms. Dot size represents gene count, color intensity reflects adjusted p-value, and odds ratio is reported on the x-axis.