20.500.12556/DiRROS-19449 Systems toxicology approach for assessing developmental neurotoxicity in Larval zebrafish Adverse outcomes that result from chemical toxicity are rarely caused by dysregulation of individual proteins; rather, they are often caused by system-level perturbations in networks of molecular events. To fully understand the mechanisms of toxicity, it is necessary to recognize the interactions of molecules, pathways, and biological processes within these networks. The developing brain is a prime example of an extremely complex network, which makes developmental neurotoxicity one of the most challenging areas in toxicology. We have developed a systems toxicology method that uses a computable biological network to represent molecular interactions in the developing brain of zebrafish larvae. The network is curated from scientific literature and describes interactions between biological processes, signaling pathways, and adverse outcomes associated with neurotoxicity. This allows us to identify important signaling hubs, pathway interactions, and emergent adverse outcomes, providing a more complete understanding of neurotoxicity. Here, we describe the construction of a zebrafish developmental neurotoxicity network and its validation by integration with publicly available neurotoxicity-related transcriptomic datasets. Our network analysis identified consistent regulation of tumor suppressors p53 and retinoblastoma 1 (Rb1) as well as the oncogene Krüppel-like factor (Klf8) in response to chemically induced developmental neurotoxicity. The developed network can be used to interpret transcriptomic data in a neurotoxicological context. cebrica ekotoksikologija genska ekspresija sistemska toksikologija matematično modeliranje neurotoksičnost true false true Angleški jezik Slovenski jezik Neznano 2024-07-18 03:50:10 2024-07-19 10:36:26 2024-07-20 04:02:59 0000-00-00 00:00:00 2021 0 0 Št. članka: 652632; Nasl. z nasl. zaslona; Opis vira z dne 16. 06. 2021; str. 1-17 vol. 12 15. June 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2021-06-15 577 1664-8021 10.3389/fgene.2021.652632 67275779 https://www.frontiersin.org/articles/10.3389/fgene.2021.652632/full 1 50e8eecf-4497-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26851 RAZ_Li_Roman_2021.pdf RAZ_Li_Roman_2021.pdf 1 D8DE12291F152A3096A95075CC5E0E97 bdf692f9b56c5f2bed8a8f00093f48ca0ae5f634178b17feffd550bc1d4a6786 505822a9-4599-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26975 Nacionalni inštitut za biologijo 0 0 0