Fig. 2: Bleomycin is a molecular initiator of fibrotic conditions.

A AOP:173 (Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis). KEs in blue were enriched by dysregulated genes under bleomycin at each of the 3 timepoints. KEs in grey were not enriched at any timepoint under bleomycin exposure. The square indicates the MIE, the triangle the AO. B The fraction of enriched KEs under Bleomycin and TGF-beta exposure that are of molecular-cellular and organ-systemic biological scale, respectively. KEs of molecular and cellular biological level were merged, presenting MIEs and early KEs of an AOP, while KEs of tissue, organ, and individual biological level were considered as of organ-systemic biological scale, presenting later KEs and AOs of an AOP. Difference between the two substances was tested by two-sided Fisher’s exact test (p value = 2e−11). C The systems of enriched KEs as recently annotated by Saarimäki et al. for bleomycin (top) and TGF-beta (bottom). D Experimental data in comparison with public RNA-Seq data sets of PF. Sixteen public data sets and in total 51 comparisons were recently curated by Inkala et al. (https://doi.org/10.5281/zenodo.10692129). Fold changes of samples of PF versus healthy controls were compared with fold changes computed for HUVEC cells exposed to bleomycin and TGF-beta, respectively. The multi-dimensional scaling plot was generated from the Euclidean distance between datasets based on the ranks of 8127 common genes according to their fold changes. BAL bronchoalveolar lavage.