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Though whole exome sequencing (WES) is the gold-standard for measuring tumor mutational burden (TMB), the development of gene-targeted panels enables cost-effective TMB estimation. With the growing number of panels in clinical trials, developing a statistical method to effectively evaluate and compare the performance of different panels is necessary. The mainstream method uses R-squared value to measure the correlation between the panel-based TMB and WES-based TMB. However, the performance of a panel is usually overestimated via R-squared value based on the long-tailed TMB distribution of the dataset. Herein, we propose angular distance, a measurement used to compute the extent of the estimated bias. Our extensive in silico analysis indicates that the R-squared value reaches a plateau after the panel size reaches 0.5 Mb, which does not adequately characterize the performance of the …