Extended Data Fig. 7: Signature of homologous recombination deficiency.

a) Associations between copy number signature attributed samples and tandem-duplicator phenotype samples, displaying -log2(Q-values) (y-axis) and log2 odds ratios (x-axis). CN17 association: OR = 6.3, Q = 3.6e-17, Fisher’s exact test. b) Prevalence (orange line) and distribution (violins) of CN17 attributions across TCGA cancer types. Blue violins are cancer types significantly enriched in CN17 compared to all others (Q < 0.05, Mann Whitney test). Points indicate the prevalence of TDP in given tumour types from the literature (Menghi et al., 2018) coloured by over- (green) or underrepresentation (gray). A half dot indicates an infinite value. c) Correlation of CN17 attribution (y-axis) with mutational status of one or more genes of the homologous recombination pathway (x-axis) in breast cancer (top, n = 589), ovarian cancer (middle, n = 309) or pan-cancer (bottom, n = 4,919). WT=wild type. Mono = Mono-allelic and Bi = bi-allelic. Two-sided Fisher’s exact test: Q-values are given above, n.s.=Q ≥ 0.05. d) Relationship between BRCA1 gene expression (x-axis) and promoter methylation (y-axis). A mean TSS1500 beta cutoff of 0.7 was chosen to indicate promoter hyper-methylation, correlating with gene silencing. e) CN17 attribution (y-axis) split by BRCA1 mutational status (x-axis) in TCGA breast cancers. WT=wild type (n = 220), Mono.=mono-allelic mutation (n = 148), Bi.=bi-allelic mutation (n = 19), Methy.=promoter hypermethylation (n = 13). Two-sided Mann-Whitney test: P-values are given above, n.s.=P ≥ 0.05. f) Association between copy number signature attribution and promoter hypermethylation of BRCA1 (beta > 0.7), displaying -log2(Q-values) (y-axis) and log2 odds ratios (x-axis) from a multivariate logistic regression model with cancer type as a covariate. g) Association between copy number signature attribution and scarHRD score, displaying -log2(Q-values) (y-axis) and log2 odds ratios (x-axis) from a Fisher’s exact test where scarHRD positivity was thresholded at >63. A half dot indicates an infinite value. h) Association between copy number signature attribution and scarHRD score, displaying -log2(Q-values) (y-axis) and difference in mean scarHRD scores (x-axis) from a Mann-Whitney test on continuous scarHRD scores. A half dot indicates an infinite value. i) Pearson’s correlation of recurrence of mapping of LOH segments of CN17 to the genome calculated for all pairwise comparisons of CN17-enriched tumour types. j) Pearson’s correlation of recurrence of mapping of CN17 to the genome from pairwise comparisons of CN17 enriched tumour types for heterozygous segments. k) Recurrence of mapped CN17 in 1 Mb windows of the human genome in all CN17 attributed BRCA, OV and UCS samples, split by LOH (blue) and heterozygous segments (orange). Tumour-suppressor genes in regions with >20% samples attributed to CN17 with LOH segments are labelled. l) Recurrence of mapped CN17 in 1 Mb windows of the human genome in all CN17 attributed SARC samples, split by LOH (blue) and heterozygous segments (orange). Tumour-suppressor genes in regions with >20% samples attributed to CN17 with LOH segments are labelled. m) Recurrence of mapped CN17 in 1 Mb windows of the human genome in all CN17 attributed STAD, LUAD, BLCA, HNSC, ESCA and LUSC samples, split by LOH (blue) and heterozygous segments (orange). Tumour-suppressor genes in regions with >20% samples attributed to CN17 with LOH segments are labelled. n) Association between copy number signature (y-axis) attribution and hypoxia score (x-axis=effect size) in a two-sided multivariate logistic regression model including cancer type as a covariate. Vertical bars indicate effect estimates, horizontal bars indicate 95% confidence intervals. P-values for significant associations (P < 0.05) are given (non-significant values can be found in Supplementary Table 7). n = 6,805 biologically independent tumours.