| Title: | Systems toxicology approach for assessing developmental neurotoxicity in Larval zebrafish |
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| Authors: | ID Li, Roman (Author)
ID Talikka, Marja (Author)
ID Belcastro, Vincenzo (Author)
ID Berg, Colette vom (Author)
ID Martin, Florian (Author)
ID Peitsch, Manuel C. (Author)
ID Hoeng, Julia (Author)
ID Županič, Anže (Author) |
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| Files: |  URL - Source URL, visit https://www.frontiersin.org/articles/10.3389/fgene.2021.652632/full
 PDF - Presentation file, download (3,16 MB)
MD5: D8DE12291F152A3096A95075CC5E0E97
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  NIB - National Institute of Biology
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| Abstract: | 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. |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Publication date: | 15.06.2021 |
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| Year of publishing: | 2021 |
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| Number of pages: | str. 1-17 |
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| Numbering: | vol. 12 |
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| PID: | 20.500.12556/DiRROS-19449  |
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| UDC: | 577 |
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| ISSN on article: | 1664-8021 |
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| DOI: | 10.3389/fgene.2021.652632 |
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| COBISS.SI-ID: | 67275779 |
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| Note: | Št. članka: 652632;
Nasl. z nasl. zaslona;
Opis vira z dne 16. 06. 2021;
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| Publication date in DiRROS: | 19.07.2024 |
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| Views: | 271 |
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| Downloads: | 181 |
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| Metadata: |    |
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