Fig. 1: Identification of EVI1 modulators from the intersection of phenotypic and genome-based approaches.

A Identification of EVI1 “Off” modulators by the integration of phenotypic and in silico gene-expression-based screen approaches. B Circos plot summarizing primary small molecule screening in EVI1^High AML cell lines. The heatmap at the external circle shows the normalized percentage of cell death (ΔPOC) for the 95th percentile for the compounds tested. The middle circos shows the compound libraries: i) Spectrum Collection (n = 1914); ii) the anti-cancer compound library (n = 343); and iii) the NDL-3000 library (n = 3035). The inner plot shows a hierarchical cluster of top candidates’ scalar fingerprints (SMILE), based on the Tanimoto similarity metric. C Dot plot showing the effects of the compound tested (n = 5292), ranked based on ΔPOC. The yellow area indicates the 95th percentile. HDAC inhibitors (HDACis) are labeled in red. D Rank-score log-scale plots for HDACis (n = 32), histamine (n = 52), glucocorticoid (n = 47), and acetylcholine receptor antagonists (n = 66). In black, the number of perturbagenes inferred in the connectivity map of which 2836 are small molecules. Compounds of interest are color-coded and expressed as a percentage relative to the entire library. E Bar plot showing the HDACis (in red) ranking in the ConnectivityMap²⁰ dataset. The tau score represents the level of similarity to the EVI1 “On” or “Off” status. F L1000FWD fireworks visualization of drug-induced signatures mimicking and reversing the differential gene expression signature generated from EVI1-silenced HNT34 (left) and from EVI1^High (n = 5) or EVI1^Low (n = 2) AML cell lines contained in the E-MTAB-2225 dataset (right). Aquamarine circles indicate small molecules causing a reverse signature EVI1 “Off”. Light violet circles indicate small molecules mimicking a signature EVI1 “On”. HDACis drug-induced signatures are indicated in green overlapping with aquamarine circles. See also Supplementary Fig. 1-2 and Supplementary Data 1.