PI3K/mTOR inhibitor gene expression signature opposes the cytoprotective signature of PTL. (A) Rank and description of PI3K or mTOR inhibitors (wortmannin, LY-294002, and sirolimus [rapamycin]) resulting from interrogation of the CMap2 database. Results are ranked according to extremeness of the negative connectivity score. The connectivity score statistic is indicated in the “Score” column. (B) Bar plot indicating the distribution of PI3K or mTOR inhibitors (wortmannin, LY-294002, or sirolimus) along the 6100 search results ordered according to similarity to PTL. Each horizontal black line indicates an instance of either wortmannin, LY-294002, or sirolimus. The green region indicates instances achieving positive connectivity scores. The gray region indicates instances with no relationship to the PTL response signature. The red region indicates instances of compounds with negative connectivity scores. The gray and green regions indicate instances of the PI3K and mTOR inhibitors class that are either unrelated to PTL or similar to PTL, respectively. The enrichment for the PI3K/mTOR inhibitor compound class is significant (P < 10⁻⁵). Results in the red region are most relevant to this screen. (C) The frequency of wortmannin, LY-294002, and sirolimus instances among the top 20 negatively connected hits arising from screens with varying PTL response signatures differing by false discovery rate cutoff. The horizontal axis indicates the false discovery rate (FDR) cutoff; the vertical axis represents the frequency of these instances.