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Additional file 2. Description of the wet-lab generation and sequencing analysis of the knockout lines. These lines were used to illustrate the functions of the MutationalPatterns package on novel real-world data and provide new biological conclusions.

Additional file 1: Additional figures, which help to illustrate the data present in this work and provide the reader with a more comprehensive understanding of the manuscript. Figure S1. Removing the DBSs and MBSs results in an improved SBS profile. Figure S2. Mutation contexts can be visualized with a river plot. Figure S3. Lesion segregation can be visualized. Figure S4. Variational Bayes NMF can be used to predict the optimal number of signatures to extract. Figure S5. Strict refitting iteratively removes signatures. Figure S6. Bootstrapped signature refitting can be visualized with a jitter plot. Figure S7. TT[C > T]CT is the most common substitution type in metastatic melanomas. Figure S8. The matrix generating functions have O(n) or better scaling. Figure S9. Benchmark of the ���mut_matrix��� function. Figure S10. Recall-precision plot of different refitting methods in MutationalPatterns. Figure S11. Western blot analysis of AHH-1 CRISPR-Cas9 edited clonal lines. Figure S12. Uncropped original version of the western blots in Fig. S11. Figure S13. SBS profiles of knockout samples.

Additional file 3: Additional tables containing extra data that can help the reader better understand the manuscript. Table S1. List of new features and bugfixes. Table S2. The potential damage of mutational signatures. Table S3. The genes used for the signature potential damage analysis. Table S4. Overview of the source of the replication timing data.

Additional file 2: Supplementary Figures.