Harmonizing tumor mutational burden analysis: Insights from a multicenter study using in silico reference data sets in clinical whole-exome sequencing (WES).

This study highlights real-world challenges in WES-based TMB analysis that need to be improved and optimized. This research will aid in the selection of more reasonable analytical procedures to minimize potential methodologic biases in estimating TMB in clinical exome sequencing tests. Harmonizing TMB estimation in clinical testing conditions is crucial for accurately evaluating patients' response to immunotherapy.