Fig 1.
Global analysis of correlations between basal gene expression and compound response.
(A) Heatmap of the Pearson correlation coefficient between genes (expression) and compounds (chemosensitivity, measured by AUC values). (B) Histogram of the number of compounds associated with each gene. The y-axis shows the number of genes associated with k compounds, where k is shown on the x-axis. (C) Histogram of the number of genes associated with each compound. The y-axis shows the number of compounds associated with k genes, where k is shown on the x-axis. (D) Histogram of the number of compounds significantly associated with each pathway (Fisher’s exact test FDR < 0.05). (E) Histogram of the number of pathways significantly associated with each compound (Fisher’s exact test FDR < 0.05).
Fig 2.
Identifying pathways associated with chemical response using PACER.
(A) Schematic description of PACER. (B) Heatmap of associations between compounds and pathways (PACER scores). Columns are compounds and rows are pathways. (C) Comparative evaluation of different methods for predicting compound-pathway associations. The ground truth used here is the pathways that contain any known target gene of the compound. (D) Number of compounds with significant overlap (p < 0.05) between pathways from LINCS and pathways from PACER, from Huang et al. 2005 and from the baseline method (Fisher’s exact test) respectively, at different levels of stringency in pathway prediction. Stringency refers to the FDR control used by the baseline method in determining significant pathways. Both PACER and the Huang et al. 2005 method were used to predict the same number of (highest scoring) pathways as the baseline method, for a fair comparison.
Table 1.
Compounds for which PACER predicted pathways with greatest AUROC.
Evaluation was performed with known targets.