Fig. 4: Signature 18-induced mutational patterns.

a Mutational signatures detected by WGS of 182 diagnosis samples, shown as proportion of mutations caused by the signature across all samples in each age group. Sample numbers are: group A, 39; B, 103; and C, 40. b Signature abundance in absolute SNVs is indicated on y-axis for five patients with matched diagnosis and relapse samples. Shared mutations (present in both diagnosis and relapse, which are thus early mutations) are indicated at left, followed by relapse-specific variants (detected only at relapse) on the right for each patient. c Differential gene expression analysis comparing signature 18-positive (n = 60) vs. signature 18-negative (n = 28) samples in 88 diagnosis samples with both WGS and RNA-Seq using Limma. Y-axis represents -log₁₀ P values; x-axis represents the log expression fold-change (mean expression difference), with genes increased in signature 18-positive samples in the positive direction (red) and genes increased in signature 18-negative samples in the negative direction (blue). Each point represents one gene, and genes with the lowest 1.9% of adjusted P values are shown in color. d Y-axis represents indicated gene’s expression in TPM, comparing signature 18-negative (n = 28) and -positive (n = 60) samples. Box, interquartile range (25th to 75th percentile); middle bar, median. Whiskers are described in R boxplot documentation (a 1.5 × interquartile range rule is used). e Proportion of SNVs caused by signature 18 in 182 diagnosis samples with WGS, comparing samples with vs. without 17q gain; or with vs. without MYCN alterations. Interquartile range, median, and whiskers are as in d. P values are by two-sided Wilcoxon rank-sum test. f t-SNE of 158 diagnosis and relapse samples with RNA-Seq (left two panels) or the subset of these with WGS (n = 96, far right). Overlaid are, from left to right: (1) ssGSEA Z-scores for the neural gene set (Supplementary Table 2) with red indicating more neural expression, (2) the 17q gain status with purple indicating no gain, and (3) proportion of mutations caused by signature 18 in each sample (Z-scores). Dotted outline is to enable comparison of a neural-enriched group between each plot. Source data are provided as a Source Data file.