Extended Data Fig. 3: Mitochondrial fitness in TILs orchestrates DNA methylation patterns.

a, Heatmaps with normalized DNA methylation beta-values for CpG islands, promoters and genes that are significantly differentially methylated between MDR/MG^hi and MDR/MG^lo samples. Regions with multiple-testing adjusted p-values less than 0.05 and with a log2 of the quotient of mean DNA methylation levels larger than 0.5 were considered significant. b, Bar plots showing the absolute number of significantly methylated and demethylated regions in MDR/MG^hi compared to MDR/MG^lo population. c, Genome pie charts reflect the distribution of significantly differentially methylated CpG islands across the genome. The distribution calculated using the PAVIS tool. d, e, Pathways from the NCI-Nature 2016 Pathway database that are significantly enriched among genes assigned to hypomethylated regions in MDR/MG^hi (d) or MDR/MG^lo (e) with indicated P-value. Enrichment was calculated using the Enrichr tool where the combined score is calculated as c = log(p-value) * z, where c is the combined score, p-value is calculated by Fisher exact test, and z is a z-score for deviation from expected rank. f, Transcription factor (TF) binding motif analysis. The plot is showing expressed TFs whose binding motifs were enriched in significantly hypomethylated regions (CpG islands and promoters) in MDR/MG^hi or MDR/MG^lo CD8⁺ TILs. NES, Normalized Enrichment Score.

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