Fig. 2

Validation of survival signatures in T47D resistance acquisition experiment. a Kaplan-Meier plots for two selected CpGs significantly associated with survival in the ER+/HER2- cohort. Patients were stratified based on the methylation levels of a risk decreasing locus CpG↓ (left; higher methylation is associated with longer survival) and a risk increasing locus CpG↑ (right; higher methylation is associated with shorter survival). H, methylation levels above median; L, methylation levels below median. Shaded areas in the Kaplan-Meier plot denote the 95% CI in the H and L strata. P-values are based on a log-rank test. b Example of a barcode enrichment plot for a TCGA BRCA survival signature in the cell line comparison of treated (LTED or TMX) samples at time point t versus WT baseline. All methylation loci are ranked from left to right by increasing log-fold change in the cell line comparison under consideration and represented by a shaded bar. Loci within the survival signature are represented by vertical bars. Red bars correspond to risk increasing loci (for example, CpG↑ indicated with a solid bar), blue bars correspond to risk decreasing loci (for example, CpG↓ indicated with a solid bar). In this example, the risk increasing loci tend to be hypermethylated (log-fold change > 0) in the treated cell line and the risk decreasing loci tend to be hypomethylated (log-fold change < 0). That is, most loci change in the same direction in the survival signature and the T47D RA experiment. c When using directional weights of 1 and − 1 for risk increasing and risk decreasing loci respectively, the blue bars are mirrored across the black dashed line at a log-fold-change of 0. In this case for a ROAST gene set test, the alternative hypothesis ‘up’ corresponds to methylation levels changing in the same direction whereas the alternative hypothesis ‘down’ corresponds to a change in the opposite direction