Detecting tumor mutation burden with RNA substrate

Development and Validation of Method for Calculating TMB Using RNA-Seq Data

Objective

[0115]This example describes the generation of a method for determining tumor mutational burden (TMB) value and rate from RNA sequencing data (e.g., paired-end RNA-seq data). The method employed an algorithm developed herein that was used to analyze the RNA sequencing data obtained from transcriptome profiling studies on tumor samples in order to determine the TMB of said samples. Given that TMB has been shown to predict response to immunotherapy treatments including PD-1 and PD-Ll inhibitors, results of this type of RNA-seq TMB analyses may also be useful for informing immunotherapeutic response. Further, the RNA-seq TMB analyses provided in this example may represent a cost-effective alternative to gold standard DNA based TMB rate determination that can be performed on tumor samples alone rather than using both tumor samples and matched normal samples, which is often done when calculating TMB using DN