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Figure A. Illustration of MMC response and pathway mutation association testing. Figure B. Barplot of MMC IC50 values in the cell line panel. Figure C. Density plot of VAF values of variants in cell line panel and control blood samples. Figure D. Effect of VAF thresholds on the number of FA/HR variants, number of FA/HR mutated cell lines, and difference in MMC IC50 values of FA/HR mutated and non-mutated cell lines. Figure E. Wilcoxon rank-sum test P-values comparing the MMC IC50 values of FA/HR mutated and non-mutated cell lines as a function of VAF thresholds. Figure F. Scatterplot number of variants against MMC sensitivity. Figure G. Scatterplot number of homozygous variants against MMC sensitivity. Figure H. Effect of MAF thresholds on the number of FA/HR variants, number of FA/HR mutated cell lines, and difference in MMC IC50 values of FA/HR mutated and non-mutated cell lines. Figure I. Wilcoxon rank-sum test P-values comparing the MMC IC50 values of FA/HR mutated and non-mutated cell lines as a function of MAF thresholds. Figure J. Selection of high VAF variants results in a significant functional endpoint association with multiple MAF thresholds. Figure K. Selection of low MAF SNPs and non-SNP variants results in a significant functional endpoint association when focusing on those with a high VAF. Figure L. Volcano plot of associations between MMC response and KEGG pathways. Figure M. PPV and Wilcoxon rank-sum test P-values for MMC sensitivity association analyses with variants selected based on REVEL and CADD deleteriousness scores. Figure N. Volcano plot of associations between MMC response and KEGG pathways based on REVEL and CADD based variant selection. Figure O. Density plot of VAF values of variants in HNSCC tumor samples and control blood samples. Table A. Capture set and genes comprising the canonical FA/HR gene set. Table B. Cell line TP53 mutation status according to literature and our variant calling. Table C. Established and candidate cancer genes in HNSCC. (PDF)