Fig. 4

Prioritization of genes based on drug sensitivity. (a). Shown is a summary of the gene score significance for the HNSCC cohort patients relative to the TCGA candidate therapeutic target genes. The EGFR gene scored highly in three patients, two of whom had amplifications of the gene via copy number. The other patient, 10058, didn’t have copy number data. Patient 10058 had EGFR as the most significant gene target and was unlikely to have had an underlying amplification as it showed mild down-regulation of EGFR from both RPPA and expression. (b). Shown is the Response Card for patient 10058. Inhibitor data is shown on the top in the form of a Zscore with negative values indicating increased sensitivity. From left to right, the scores of the top genes by significance are shown along with SYK which was a target of the most significant drug. In addition, a heatmap displays the drug target data from Targetome. Finally, any mutations (black rectangle) in these genes are shown along with RPPA and expression from the tumor cell culture models after being centered/scaled to Zscore values. If available, copy number data is also displayed. (c) Using a network propagation approach we prioritized the patient’s somatic mutations and the results are displayed as a barplot where the resulting prioritization score is on the Y-axis and corresponding gene is on the X-axis. (d) The mutations that scored highly in the prioritization (blue ovals) were seen to interact with EGFR and the other significant gene targets (green rectangles) either directly or indirectly in a network context.