Fig. 1.

The landscape of Mouse Single Base Substitution (mSBS) signatures induced by chemical exposures and endogenous mutagenic processes. A, Mutational burden across the collection of lung, liver, kidney and forestomach tumours sequenced in this study. The central line represents the median, the lower line is the first quantile (Q₁) and the upper line is the third quantile (Q₃). The upper whisker extends from Q₃ to 1.5 times the inter-quartile range (IQR), the lower whisker extends from Q ₁to 1.5 times the IQR. Cobalt and vanadium pentoxide in lung and TCP in liver have significantly more substitutions than the corresponding spontaneous tumours (FDR-corrected one-sided Mann-Whitney U-test). B, Comparison of mouse substitution signatures to human signatures. *SBS17=SBS17a and SBS17b. C, Contribution of mSBS signatures across lung, liver, kidney and forestomach tumours, grouped by chemical exposure. The size of the dots corresponds to the percentage of samples in each category having a minimal contribution level of 10% from the signature. The colour represents the mean relative contribution for the samples where the signature contribution is ≥10%. Of note, mSBS_N3 was detected in a spontaneous liver tumour just below this threshold. D, Profile of the catalogue of mSBS Signatures. E, Common and unique mutational signatures in liver and forestomach tumours from mice exposed to TCP. mSBS19 (dark green) is present in liver and forestomach tumours. mSBS42 and mSBS_N2 (light green) are present only in forestomach tumours. Treatment dose is shown. F, Common and unique mutational signatures in lung, liver and kidney tumours from mice exposed to vinylidene chloride (VDC). The mutational burden varied greatly based on tissue. For clarity, mSBS5 (light red) is shown at the top of the stacked bars and mSBS18 (dark red) towards the bottom. M and F refer to male and female, respectively.