PUBLICATION
Computational approach for collection and prediction of molecular initiating events in developmental toxicity
- Authors
- Cendoya, X., Quevedo, C., Ipiñazar, M., Planes, F.J.
- ID
- ZDB-PUB-200429-16
- Date
- 2020
- Source
- Reproductive toxicology (Elmsford, N.Y.) 94: 55-64 (Journal)
- Registered Authors
- Ipiñazar, Maitane, Quevedo, Celia
- Keywords
- Computational, Developmental toxicity, Mechanism of action, Statistical model
- MeSH Terms
-
- Animals
- Computational Biology
- Databases, Factual*
- Embryo, Nonmammalian/drug effects*
- Embryonic Development/drug effects
- Humans
- Models, Animal
- Teratogens/toxicity*
- Toxicity Tests*
- Zebrafish*
- PubMed
- 32344110 Full text @ Reprod. Toxicol.
Citation
Cendoya, X., Quevedo, C., Ipiñazar, M., Planes, F.J. (2020) Computational approach for collection and prediction of molecular initiating events in developmental toxicity. Reproductive toxicology (Elmsford, N.Y.). 94:55-64.
Abstract
Developmental toxicity is defined as the occurrence of adverse effects on the developing organism as a result from exposure to a toxic agent. These alterations can have long-term acute effects. Current in vitro models present important limitations and the evaluation of toxicity is not entirely objective. In silico methods have also shown limited success, in part due to complex and varied mechanisms of action that mediate developmental toxicity, which are sometimes poorly understood. In this article, we compiled a dataset of compounds with developmental toxicity categories and annotated mechanisms of action for both toxic and non-toxic compounds (DVTOX). With it, we selected a panel of protein targets that might be part of putative Molecular Initiating Events (MIEs) of Adverse Outcome Pathways of developmental toxicity. The validity of this list of candidate MIEs was studied through the evaluation of new drug-target relationships that include such proteins, but were not part of the original database. Finally, an orthology analysis of this protein panel was conducted to select an appropriate animal model to assess developmental toxicity. We tested our approach using the zebrafish embryo toxicity test, finding positive results.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping