Abstract
The current challenge in cancer research is to increase the resolution of driver prediction from gene-level to mutation-level, which is more closely aligned with the goal of precision cancer medicine. Improved methods to distinguish drivers from passengers are urgently needed to dig out driver mutations from increasing exome sequencing studies. Here, we developed an ensemble method, AI-Driver (AI-based driver classifier, https://github.com/hatchetProject/AI-Driver), to predict the driver status of somatic missense mutations based on 23 pathogenicity features. AI-Driver has the best overall performance compared with any individual tool and two cancer-specific driver predicting methods. We demonstrate the superior and stable performance of our model using four independent benchmarks. We provide pre-computed AI-Driver scores for all possible human missense variants (http://aidriver.maolab.org/) to identify driver mutations in the sea of somatic mutations discovered by personal cancer sequencing. We believe that AI-Driver together with pre-computed database will play vital important roles in the human cancer studies, such as identification of driver mutation in personal cancer genomes, discovery of targeting sites for cancer therapeutic treatments and prediction of tumor biomarkers for early diagnosis by liquid biopsy.