DOTS-Finder workflow. Illustration of the three main steps and the databases used to identify driver genes. Starting from the top left, a Mutation Annotation Format (MAF) file is taken as input. This file can encompass patients with any particular kind of tumor or any stratification of homogeneous samples under specific criteria (for example, smoker patients with lung cancer, patients aged <50 years, and so on). The workflow includes the following three steps (green arrows): 1) preliminary step - the dataset is filtered, reannotated and aggregated by gene (from top-left to bottom-left); 2) functional step - Tumor Suppressor Gene Score (TSG-S) and OncoGene Score (OG-S) are calculated (from bottom-left to bottom-right); 3) frequentist step - four statistical tests are run on genes that exceed the TSG-S and OG-S thresholds (from bottom-right to top-right). The center panel (Data Integration) lists the external sources used by DOTS-Finder. CDD, Conserved Domain Database.