This package provides a systematic bioinformatics tool to develop a new pathway-based gene panel for tumor mutational burden (TMB) assessment (pathway-based tumor mutational burden, PTMB), using somatic mutations files in an efficient manner from either The Cancer Genome Atlas sources or any in-house studies as long as the data is in mutation annotation file (MAF) format. Besides, we develop a multiple machine learning method using the sample's PTMB profiles to identify cancer-specific dysfunction pathways, which can be a biomarker of prognostic and predictive for cancer immunotherapy.