Probabilistic Mixture Models Improve Calibration of Panel-derived Tumor Mutational Burden in the Context of both Tumor-normal and Tumor-only Sequencing.

A probabilistic mixture model better models the nonlinearity and heteroscedasticity of the data as compared with linear regression. Tumor-only panel data are needed to properly calibrate tumor-only panels to exomic TMB. Leveraging the uncertainty of point estimates from these models better informs cohort stratification in terms of TMB.