| Title: | From causal networks to adverse outcome pathways : a developmental neurotoxicity case study |
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| Authors: | ID Ramšak, Živa (Author)
ID Modic, Vid (Author)
ID Li, Roman A. (Author)
ID Berg, Colette vom (Author)
ID Županič, Anže (Author) |
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| Files: |  URL - Source URL, visit https://www.frontiersin.org/articles/10.3389/ftox.2022.815754/full
 PDF - Presentation file, download (1,65 MB)
MD5: E74EC9C24945182843AA101CD52C49B9
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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: | 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. |
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| Keywords: | systems toxicology, adverse outcome pathway, casual network, toxicological network, neurotoxicity |
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| Publication version: | Version of Record |
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| Publication date: | 07.03.2022 |
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| Year of publishing: | 2022 |
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| Number of pages: | str. 1-18 |
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| Numbering: | Vol. 4 |
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| PID: | 20.500.12556/DiRROS-19371  |
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| UDC: | 60 |
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| ISSN on article: | 2673-3080 |
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| DOI: | 10.3389/ftox.2022.815754 |
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| COBISS.SI-ID: | 100245251 |
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| Note: | 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;
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| Publication date in DiRROS: | 16.07.2024 |
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| Views: | 315 |
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| Downloads: | 203 |
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| Metadata: |    |
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