Fig. 5: C₂H₂ family members enrich relevant AOPs.

a–c, Top ten enriched MIEs, key events and adverse outcomes, with their respective adjusted P value (expressed as minus the logarithm of the value). TLR, toll-like receptor; ACE2, angiotensin-converting enzyme 2; TNF, tumour necrosis factor; EGFR, epidermal growth factor receptor; SLE, systemic lupus erythematosus; PPAR, peroxisome proliferator-activated receptor; IL-1, interleukin-1; GR, glucocorticoid receptor; SD, Sprague–Dawley; AR, androgen receptor; NR, nipple retention.; AP-1, activator protein 1; PIN-1, peptidylprolyl cis/trans isomerase NIMA-interacting 1; EMT epithelial mesenchymal transition. d, Top 20 enriched AOPs; JNK, jun N-terminal kinase; TGF, transforming growth factor. Besides the classical enrichment, we filtered pathways according to the proportion of individual key events enriched and discarded the ones in which less than one-third of the pathway is covered. e, Example of the ‘endocytic lysosomal uptake leading to liver fibrosis’ AOP, enriched by the regulatory model we identified. MIEs and adverse outcomes are represented in blue and green, respectively. Events reported as transparent do not pass the significance threshold (P < 0.05). f, Example of the ‘Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis’ AOP, enriched by the regulatory model we identified. Graphical annotation is the same as in e. The statistical significance in a–e was determined with a Fisher test, and multiple comparisons adjustment method was performed with the Bonferroni correction.