Gene set analysis was performed with the piano R package (v.1.8.2) using the Mean method (36), with 1000 permutations and with minimum and maximum gene sets of 15 and 500, respectively, against the 50 hallmark (h) gene sets from the MSigDB (v.6.1). Resulting gene sets with a nominal P value of 0.05 were considered significant. Distinct directional network maps were visualized with the piano R package.

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