Extended Data Fig. 1. Identification and clinical associations of clustered events.

a, Schematic depiction for separating clustered mutations for a sample. b, Subclassification of clustered substitutions and indels. Expected IMD derived using steps 2 and 3 (a). c, Distribution of indels present in a single clustered event. d, Distribution of clustered substitutions (left) and indels (right) across cancers with less than 10 samples subclassified into different categories. e, Correlations between TMB of each sample, the TMB within the exome, or the TMB for each class of clustered substitutions (left) and indels (right). f, Distribution of VAFs for all clustered substitution classes (left; DBS: 1,215 samples; MBS: 851; omikli:1,466; kataegis: 1,108; other: 335) with the average fold enrichment compared against non-clustered mutations (right). For each boxplot, the middle line reflects the median, the lower and upper bounds correspond to the first and third quartiles, and the lower and upper whiskers extend from the box by 1.5x the inter-quartile range (IQR). g, Kaplan–Meier curves between samples with high (top 80^th percentile) and low (bottom 20^th percentile) clustered substitution (left) or indel (right) burdens in PCAWG ovarian cancer. h, Cox regressions performed for PCAWG cancer types while correcting for age (n = 20 upper and n = 21 lower clustered substitutions; n = 49 upper and n = 49 lower clustered indels). i, Kaplan–Meier survival curves for TCGA cancer types with a differential patient outcome associated with the detection of any clustered mutations. j, k, Cox regressions performed for TCGA samples while correcting for age (j) and total mutational burden (k) (OV: n = 111 upper, n = 159 lower clustered substitutions; UCEC: n = 322 upper, n = 64 lower; ACC: n = 24 upper, n = 67 lower). PCAWG ovarian cancers were included in k. Centre of measure for each Cox regression reflects the log₁₀(Hazards ratios) with the 95% confidence intervals in h–k).