Figure 2. Neurodevelopmental impact of sildenafil unveiled by multi-omics.

(A) Dot plot highlighting top ten enriched Gene Ontology (GO) biological processes in LS NPCs (ATP6_2, ATP6_4, ATP6_5, ATP6_7) upon sildenafil treatment (10 μM for 16 h) based on transcriptomics. (B) Dot plot highlighting top ten enriched GO biological processes in LS NPCs (ATP6_2, ATP6_4, ATP6_5, ATP6_7) upon sildenafil treatment (10 μM for 16 h) based on proteomics. (C). Enrichment analysis for 724 reversed molecules by sildenafil based on multi-omics integration. GO biological processes for reversed molecules with logarithmic fold change (logFC)>0 after sildenafil treatment. (D) 3D multi-omics network of the sildenafil signature in LS NPCs. Size of dots defines their cetntrality in the network; color of dots indicates their logFC value. (E) Expression of putative sildenafil-responsive genes identified in the literature in LS NPCs (ATP6_2, ATP6_4, ATP6_5, ATP6_7) compared to control NPCs (CTRL_1, CTRL_2, CTRL_3, CTRL_4) (disease signature) and in DMSO-treated LS NPCs (ATP6_2, ATP_4, ATP6_5, ATP6_7) compared to sildenafil treated LS NPCs (sildenafil signature) based on bulk transcriptomics. (F-G) Network analysis for the HOXA5 hub and associated pathways in the disease signature and sildenafil signature.