Fig. 4: Trabectedin-induced DNA break counts correlate with gene expression levels.

DNA break count on each strand of protein-coding genes in U2OS WT (a), CSB-KO (b), XPC-KO (c) and XPA-KO (d) after 2 h exposure to trabectedin and subsequent 2 h recovery versus gene expression level in unexposed U2OS WT. ρ: Spearman correlation coefficient calculated for continuous (not tiered) data of gene expression and DNA break count (correlation analysis for all replicates in Supplementary Fig. 5h), n = 16,740. Heatmaps: the color of a hexagonal bin reflects the gene count. TPM, transcripts per million transcripts. Box plots: gene expression was categorized in tiers via percentiles shown by vertical lines in the heatmaps; boxes are interquartile ranges, internal horizontal lines are medians, circular markers are means, whiskers extend to the furthest datapoint within 1.5x interquartile range, datapoints beyond are shown as small markers. Number of genes per tier and number of genes beyond the maximal y-axis value are provided in Methods. Presented data: one biological replicate of drug exposure per cell line. Mean DNA break count of protein-coding genes in U2OS WT (e), CSB-KO (f), XPC-KO (g) and XPA-KO (h) after 2h exposure to trabectedin or vehicle and subsequent 2h recovery versus gene expression level in unexposed U2OS WT. Presented data: multiple biological replicates. Gene expression tiers are described in a–d. Number of genes per tier are provided in Methods. The internal plots zoom in on the y-axis. a-h: arb. unit, arbitrary unit: Methods describe DNA break count normalization. Source data are provided as a Source Data file.