SEAZIT ontologies, database, and data analysis pipeline
The zebrafish embryo is a useful alternative research model for assessing the effects of substances on growth and development. However, cross-laboratory developmental toxicity outcomes can vary due to lack of standardization both in laboratory procedures and terminology used to describe outcomes. Thus, reported developmental defects in zebrafish may not be directly comparable between laboratories. To enable broader adoption of zebrafish for toxicological screening NIEHS established the Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) program.
Discussions among scientists participating in SEAZIT considered how variability in results could be addressed by implementing standardized nomenclature systems known as ontologies. A collaborative exercise was conducted to evaluate how the application of ontologies improved data consistency (Thessen et al. 2022). Analysis of the results suggested that the use of ontology terms increased consistency and decreased ambiguity, and that utilizing a common data standard should reduce the heterogeneity of reported terms and potentially increase agreement and repeatability between different laboratories.
A key element of SEAZIT is an interlaboratory study to investigate how experimental protocol differences can influence chemical-mediated effects on developmental toxicity. Three laboratories were provided a common and blinded set of 42 substances to evaluate chemical effects on developmental toxicity in the embryonic zebrafish model. Laboratory work was completed in 2022, and a paper has been published (Hsieh et al. 2023) describing the relational database developed to store the data, which features harmonization of the above-described ontologies for altered phenotype endpoints, and the data analysis pipeline. Data are available in the NIEHS CEBS data resource, and a web application is being developed to allow users to interactively explore the data. A second paper describing the study design is being prepared for publication in 2024.