Extended Data Fig. 7: Haplotype resolved lesion segregation in F1 mice. | Nature Genetics

Extended Data Fig. 7: Haplotype resolved lesion segregation in F1 mice.

From: Single-mitosis dissection of acute and chronic DNA mutagenesis and repair

Extended Data Fig. 7

a, Percentage of mapped reads to a specific genome. Each bar represents a tumor where brown depicts Mus castaneus specific reads and gold C3H. Mean haplotype-specific reads for all 6 libraries is denoted by the vertical dashed line. Colored boxes on the left denote which mouse the tumor was isolated from. b, Chromosome specific mapping rate for one of the tumors in (a). Note Mus castaneus specific mapping to the X. c, Read coverage per mutation in each library. Horizontal red dashed line represents 20x coverage. Colored boxes below denote mouse of origin as in (a). Boxplot elements are as described in Fig. 3c. d, Number of mutations per tumor. Colors and symbols as in panel (a). e, Genomic stability of F1 tumors. Read counts in 10 kb windows for a representative tumor. Y axis represents log2 counts subtracted from the mean of all bins. Horizontal green line represents no difference, while horizontal red lines depict duplication or haploid content. f, Percent of out-of-phase mutations. The proportion of mutations with a reference T or A base was calculated within changepoint derived segments (see Methods). In the haplotype-agnostic analysis (gray points), out of phase represents the mean amount of mutations with an identity opposite to its segment. As an example, mutations at A bases when mutations within the segment are predominantly at T bases (n = 6 tumor genomes). For segments to be considered ‘phased’ in the haplotype-agnostic analysis, at least 80% of mutations in that segment had to be of a single type. Haplotype resolved whole-genome mutations with opposing identity are shown in red (n = 12, 6 genomes with 2 alleles each), and X chromosome localized mutations in black (n = 6). Horizontal lines represent the mean of each set of points. g, Left: Correlation between T < > A phasing and C < > G phasing in a single tumor within 10 mb windows. C and T mutations (as well as G and A) share phase within a single tumor. Right: comparison between T < > A phasing in tumor 2 to C < > G phasing in tumor 1. h, Comparison of T < > A phasing across all 6 tumors, as measured by Pearson correlation for phasing in 10 mb bins. i, Boxplot of correlation of T < > A phasing between all non-self correlations (n = 15) as in (h), as well as random expectation of phasing correlation seen after mixing bins for all 6 tumors (n = 15). The solid middle line represents the median, the gray box depicts the interquartile range between the 1st and 3rd quartile, while the whiskers define the minima and maxima. Outliers are shown as points. j, Heatmap of T < > A phasing (x axis) with C < > G phasing (y axis) between and within tumors. Mouse of origin are colored as in (a).

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