Fig. 1

Accuracy and precision of comprehensive genomic profiling for assessing tumor mutation burden. a Comparison of tumor mutation burden measured by whole exome sequencing versus comprehensive genomic profiling. Tumor mutation burden (mutations/Mb) was measured in 29 samples by whole exome sequencing of matched tumor and normal samples and by comprehensive genomic profiling (see “Methods” for more details). The line y = x is plotted in red. b Tumor mutation burden measured by comprehensive genomic profiling in 60 pairs of replicates. The line y = x is plotted in red. c Results of simulations of percentage deviation from actual TMB when sampling different numbers of megabases sequenced. Median observed deviation is shown in black and 10% and 90% confidence interval are shown in grey. Lines are smoothed using a cubic smoothing spline with smoothing parameter = 0.6. Left: results of simulations with TMB equal to 100 mutations/Mb. Center: results of simulations with TMB equal to 20 mutations/Mb. The median line was smoothed with smoothing parameter = 0.8. Right: results of simulations with TMB equal to 10 mutations/Mb. The median line was smoothed with smoothing parameter = 0.8