20.500.12556/DiRROS-19371 From causal networks to adverse outcome pathways a developmental neurotoxicity case study The last decade has seen the adverse outcome pathways (AOP) framework become one of the most powerful tools in chemical risk assessment, but the development of new AOPs remains a slow and manually intensive process. Here, we present a faster approach for AOP generation, based on manually curated causal toxicological networks. As a case study, we took a recently published zebrafish developmental neurotoxicity network, which contains causally connected molecular events leading to neuropathologies, and developed two new adverse outcome pathways: Inhibition of Fyna (Src family tyrosine kinase A) leading to increased mortality via decreased eye size (AOP 399 on AOP-Wiki) and GSK3beta (Glycogen synthase kinase 3 beta) inactivation leading to increased mortality via defects in developing inner ear (AOP 410). The approach consists of an automatic separation of the toxicological network into candidate AOPs, filtering the AOPs according to available evidence and length as well as manual development of new AOPs and weight-of-evidence evaluation. The semiautomatic approach described here provides a new opportunity for fast and straightforward AOP development based on large network resources. systems toxicology adverse outcome pathway casual network toxicological network neurotoxicity sistemska toksikologija pot negativnega izida vzorčno omrežje toksikološko omrežje nevrotoksičnost true false true Angleški jezik Slovenski jezik Neznano 2024-07-16 16:36:39 2024-07-16 16:36:39 2024-07-17 03:59:16 0000-00-00 00:00:00 2022 0 0 Opis vira z dne 9. 3. 2022; Nasl. z nasl. zaslona; Soavtorji: Vid Modic, Roman A. Li, Colette vom Berg, Anze Zupanic; Št. članka: 815754; str. 1-18 Vol. 4 7. Mar. 2022 0000-00-00 Zaloznikova NiDoloceno NiDoloceno 0000-00-00 0000-00-00 2022-03-07 60 2673-3080 10.3389/ftox.2022.815754 100245251 https://www.frontiersin.org/articles/10.3389/ftox.2022.815754/full 1 0db62dc8-4370-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26719 RAZ_Ramsak_Ziva_2022.pdf RAZ_Ramsak_Ziva_2022.pdf 1 E74EC9C24945182843AA101CD52C49B9 e28eca3d365d6ae9ce60658d772da6a4cda3d66a35ebc580eeef575e1b4d071a 91652346-4370-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26720 Nacionalni inštitut za biologijo 0 0 0