Fig. 2

The iCAGES package as three layers. The input file contains all variants identified from the patient; it can be either in ANNOVAR input format or in VCF format. The first layer of iCAGES prioritizes mutations. It computes three different feature scores for annotating the gene, including the radial SVM score for each of its point coding mutations, CNV normalized peak score for each of its structural variations, and FunSeq2 score for each of its point non-coding mutations. The second layer of iCAGES prioritizes cancer driver genes. It takes three feature scores from the first layer, generates the corresponding Phenolyzer score for each mutated gene and computes a LR score for this gene (iCAGES gene score). The final level of iCAGES prioritizes targeted drugs. It first queries the DGIdb and FDA drug database for potential drugs that interact with mutated genes and their neighbors. Next, it calculates the joint probability for each drug being the most effective (iCAGES drug score) from three feature scores, which are iCAGES gene scores for its direct/indirect target, normalized BioSystems probability measuring the maximum relatedness of a drug’s direct target with each mutated gene (final target), and PubChem active probability measuring the bioactivity of the drug. The final output of iCAGES consists of three major elements, a prioritized list of mutations, a prioritized list of genes with their iCAGES gene scores, as well as a prioritized list of targeted drugs with their iCAGES drug scores