Network potential identifies therapeutic miRNA cocktails in Ewing sarcoma
Fig 4
TRIM25, APP, ELAVL1, AND RNF4, and XPO1 are the top protein targets ranked by predicted disruption following in silico repression.
Panel A: Box and whisker plot describing the change in network potential following in silico repression for each of the top 50 proteins. 99.99% confidence interval from the permutation test are displayed alongside the box and whisker plots. It is notable that EWSR1, the kinase associated with Ewing sarcoma development, is considered highly influential in the cell signaling network by this method, even in comparison to the computed null distribution. Genes that have previously been causally implicated in cancer according to the Cosmic database are highlighted in red [41]. Essential housekeeping genes (excluding those that are causally implicated in cancer) are highlighted in blue. The heat-map on the x-axis corresponds to the protein-mRNA correlation of each gene in the Cancer Cell Line Encyclopedia [34]. Panel B: Histogram depicting the distribution of Pearson correlation between mRNA expression and protein expression from the Cancer Cell Line Encyclopedia for all nodes included in our final Ewing sarcoma cell signaling networks. Proteins that were ranked particularly highly in panel A were labeled in panel B. Pancel C: Bar chart describing the most frequently observed genes among the top projected targets for the 15 patient tumor samples we analyzed. There was very little overlap in top projected targets between the cell line and patient data, reflecting the transcriptional heterogeneity present in Ewing Sarcoma.