Fig. 2

Identification of target TFs by ChIPEA. a Distribution of AUROC and AUPR scores for each chemical–TF association predicted using ChIPEA. Red and black horizontal lines inside the box represent mean and median scores, respectively, and global scores are noted beside the violin plots. b Distribution of AUROC scores by chemical class according to the first level of the Anatomical Therapeutic Chemical classification system (ATC code). Chemicals are assigned the following ATC codes. A: alimentary tract and metabolism; B: blood and blood-forming organs; C: cardiovascular system; D: dermatologicals; G: genitourinary system and sex hormones; H: systemic hormonal preparations, excluding sex hormones and insulins; J: anti-infectives for systemic use; L: antineoplastic and immunomodulating agents; M: musculoskeletal system; N: nervous system; P: anti-parasitic products, insecticides and repellents; R: respiratory system; S: sensory organs; V: various; NaN: not assigned. The numbers of chemicals assigned to each ATC code are noted above the violin plots. Mean, median, and global AUROC scores are shown with red, black, and blue horizontal lines, respectively. c Predicted target TFs of five representative chemicals. Dots indicate individual TFs and are colored orange if they matched chemical–target associations recorded in KEGG DRUG. AUROC scores indicating the accuracy of the chemical–TF association inference are shown in parentheses following the names of the chemicals. Enrichment scores (−log₁₀[p-value]) were calculated using the two-tailed Fisher’s exact test. The null hypothesis is that the intersection of the reference peaks for up-regulated genes occurs in the same proportion as for those with down-regulated genes. Fold enrichment (detailed in Methods) was calculated using the same ChIP-seq data and the following equation: (overlaps/up-regulated genes)/(overlaps/down-regulated genes)