PUBLICATION
From Causal Networks to Adverse Outcome Pathways: A Developmental Neurotoxicity Case Study
- Authors
- Ramšak, Ž., Modic, V., Li, R.A., Vom Berg, C., Zupanic, A.
- ID
- ZDB-PUB-220318-5
- Date
- 2022
- Source
- Frontiers in toxicology 4: 815754 (Journal)
- Registered Authors
- Li, Roman, vom Berg, Colette
- Keywords
- adverse outcome pathway, causal network, neurotoxicity, systems toxicology, toxicological network
- MeSH Terms
- none
- PubMed
- 35295214 Full text @ Front Toxicol
Citation
Ramšak, Ž., Modic, V., Li, R.A., Vom Berg, C., Zupanic, A. (2022) From Causal Networks to Adverse Outcome Pathways: A Developmental Neurotoxicity Case Study. Frontiers in toxicology. 4:815754.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping