Matches in SemOpenAlex for { <https://semopenalex.org/work/W4285013595> ?p ?o ?g. }
- W4285013595 abstract "Abstract Mechanistic toxicology has emerged as a powerful framework to inform on the safety of chemicals and guide the development of new safe-by-design compounds. Although toxicogenomics provides support towards mechanistic evaluation of chemical exposures, the implementation of toxicogenomics-based evidence in the regulatory setting is still hindered by uncertainties related to the analysis and interpretation of such data. Adverse Outcome Pathways (AOPs) are multi-scale models that link chemical exposures to adverse outcomes through causal cascades of key events (KEs). The use of mechanistic evidence through the AOP framework is actively promoted for the development of new approach methods (NAMs) and to reduce animal experimentation. However, in order to unleash the full potential of AOPs and build confidence into toxicogenomics, robust and unified associations between KEs and patterns of molecular alteration need to be established. Here, we hypothesised that systematic curation of molecular events associated with KEs would enable the modelling of AOPs through gene-level data, creating the much-needed link between toxicogenomics and the systemic mechanisms depicted by the AOPs. This, in turn, introduces novel ways of benefitting from the AOP concept, including predictive models, read-across, and targeted assays, while also reducing the need for multiple testing strategies. Hence, we developed a multi-step strategy to annotate the AOPs relevant to human health risk assessment. We show that our framework successfully highlights relevant adverse outcomes for chemical exposures with strong in vitro and in vivo convergence, supporting chemical grouping and other data-driven approaches. Finally, we defined and experimentally validated a panel of robust AOP-derived in vitro biomarkers for pulmonary fibrosis." @default.
- W4285013595 created "2022-07-12" @default.
- W4285013595 creator A5003627670 @default.
- W4285013595 creator A5025810407 @default.
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- W4285013595 creator A5032173283 @default.
- W4285013595 creator A5037963521 @default.
- W4285013595 creator A5041632230 @default.
- W4285013595 creator A5054987771 @default.
- W4285013595 creator A5059827878 @default.
- W4285013595 creator A5088226075 @default.
- W4285013595 date "2022-07-10" @default.
- W4285013595 modified "2023-10-14" @default.
- W4285013595 title "Molecular annotation of AOPs guides the development of the next generation mechanistic chemical safety assessment and new approach methods" @default.
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