Extended Data Fig. 8: Genomic and clinical correlates.

a) Correlation between Shannon’s diversity index of signature proportions in samples, and driver gene mutation status. Effect size (log2 odds ratio, y-axis) and significance (-log2 Q-value, y-axis) are displayed. Driver genes with |log2(OR)|>1 and Q < 0.05 are labelled. TP53 association: OR = 3.65, Q = 3.0e- 51. b) Pan-cancer copy number signature attribution in 36 TP53 mutant RPE1 single cell sequenced cells (Mardin et al., 2020). Left: input profile summaries (red). Right: copy number signature attribution (blue). c) Heatmaps of copy number signatures identified across the spectrum of Li-Fraumeni Syndrome (LFS) associated cancers and somatic TP53 mutant cancers. Colour indicates the strength of signature attribution. Somatic=somatic TP53 mutant cancers, LFS=germline TP53 mutant cancers. d) Heatmap of copy number signature attribution (left) and driver gene mutation status (right) for all COAD samples, split by microsatellite instability status. Driver gene mutations are coloured orange or blue for genes that are positively (OR > 1, Q < 0.05) or negatively (OR < 1, Q < 0.05) associated with MSI status respectively, and grey for genes that are not associated with MSI status (q≥0.05). Association between CN1 or CN2 and MSI status: OR = 1.8 and 0.21, P = 0.03 and 7.7e-9 respectively, Fisher’s exact test. e) Correlations between leukocyte fraction (y-axis, split by median value per tumour type) and copy number signature attribution (x-axis). Effect size given as log2(OR) (colour) and significance given as Q-values (size) are displayed. Only associations with |log2(OR)|>1 and Q < 0.05 are shown. Associations were tested with a logistic regression model with leukocyte fraction as the dependent variable and tumour purity and copy number signature attribution (binarized) as independent variables (purity associations not shown). f) Heatmap of copy number signature attribution (left) and driver gene mutation status (right) for all UCEC samples, split by microsatellite instability status. Driver gene mutations are coloured orange or blue for genes that are positively (OR > 1, Q < 0.05) or negatively (OR < 1, Q < 0.05) associated with MSI status respectively, and grey for genes that are not associated with MSI status (q≥0.05). Association between CN1 or CN2 and MSI status: OR = 0.17 and 2.6, P = 1.1e-10 and 7.0e-4 respectively, Fisher’s exact test. g) Association between HPV status and copy number signature attribution. X-axis=effect size (log odds ratio), y-axis=significance (-log2 Q-value). Fisher’s exact test. A half dot indicates an infinite value. h) Association between hypoxia score (y-axis) and HPV status (x-axis). Two-sided Mann-Whitney test. n = 259 biologically independent tumour samples. i) Associations between copy number signatures (x-axis) and driver gene copy number alteration status (y-axis, amplification for oncogenes, homozygous deletion for tumour-suppressor genes) across each TCGA tumour type (panels). Effect size (log2 odds ratio, colour), and significance level (-log2 Q-value, size) from a Fisher’s exact test are displayed. j) Associations between copy number signatures and TCGA Asian ethnicity, using TCGA White ethnicity as a reference. k) Associations between copy number signatures and TCGA Black ethnicity, using TCGA White ethnicity as a reference. l) Correlation between copy number signature (x-axis) attribution and sex (left), smoking status (middle) and drinking status (right) across TCGA samples. Strength of correlation is indicated by colour (orange=anti-correlated, blue=correlated), Q-value is indicated by size of point. m) Association between copy number signatures (y-axis) and median dichotomised age at diagnosis for individual cancer types (x-axis). Strength of correlation is indicated by colour (orange=negatively associated, blue=positively associated), Q-value is indicated by size of point. Only tumour types/copy number signature combinations with a significant (Q < 0.05) association with age at diagnosis are shown.