Extended Data Fig. 9: Proteome fingerprints can be maintained across a concentration range.

(a) Experimental design for a compound rescreen, which compares the proteome fingerprints of 8 tool compounds at two doses; 10 μM versus 500 nM or 1 μM, to those from the primary 875 compound MOA dataset (referred here as the reference dataset). **** There are no compounds with significant correlation (p > 0.38) to 500 nM Simvastatin (b) Study results depicting treatment concentration, identity of top correlated compounds from the reference dataset, and a heatmap of Pearson correlations (r) between proteome fingerprints from the indicated compound/concentration and the same compound from the reference dataset. (c) Table of the top six most similar compounds from the MOA reference dataset for the two treatment concentrations of JQ-1 from the rescreen experiment. (d) Scatterplots for a representative set of compounds from the rescreen experiment (y-axes) plotted against the indicated compound from the reference MOA dataset (x-axes). All values are Log2(fold change – compound vs. DMSO). The y = x line is shown on each plot to observe the relative trend in the relationship different concentrations and the reference proteome fingerprint. (e) Scatterplots for simvastatin, a HMGCR inhibitor, at two concentrations relative to the reference. This compound upregulates its target at both 500 nM and 10 μM.