학술논문

Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT): Developing a Data Analysis Pipeline for the Assessment of Developmental Toxicity with an Interlaboratory Study
Document Type
article
Source
Toxics, Vol 11, Iss 5, p 407 (2023)
Subject
danio rerio
developmental toxicity testing
embryonic development
data analysis pipeline
phenotype ontology
developmental toxicants
Chemical technology
TP1-1185
Language
English
ISSN
2305-6304
Abstract
The embryonic zebrafish is a useful vertebrate model for assessing the effects of substances on growth and development. However, cross-laboratory developmental toxicity outcomes can vary and reported developmental defects in zebrafish may not be directly comparable between laboratories. To address these limitations for gaining broader adoption of the zebrafish model for toxicological screening, we established the Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) program to investigate how experimental protocol differences can influence chemical-mediated effects on developmental toxicity (i.e., mortality and the incidence of altered phenotypes). As part of SEAZIT, three laboratories were provided a common and blinded dataset (42 substances) to evaluate substance-mediated effects on developmental toxicity in the embryonic zebrafish model. To facilitate cross-laboratory comparisons, all the raw experimental data were collected, stored in a relational database, and analyzed with a uniform data analysis pipeline. Due to variances in laboratory-specific terminology for altered phenotypes, we utilized ontology terms available from the Ontology Lookup Service (OLS) for Zebrafish Phenotype to enable additional cross-laboratory comparisons. In this manuscript, we utilized data from the first phase of screening (dose range finding, DRF) to highlight the methodology associated with the development of the database and data analysis pipeline, as well as zebrafish phenotype ontology mapping.