BY OUR PLATFORMS
BY THERAPEUTIC AREA
11 March 2022
The article is the result of a collaborative exercise undertaken by the Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT, 2017), under the umbrella of the National Toxicology Program (NTP). The aim was to evaluate how the application of standardized phenotype terminology in zebrafish toxicity testing can improve data consistency for a broader adoption of the zebrafish model for toxicological screening.
The small size and rapid development of the zebrafish make it a useful vertebrate model for assessing the potential effects of substances on growth and development using high-throughput screening methods. Additionally, zebrafish embryos are not considered an experimental animal until they begin to feed themselves (5 to 6 days post fertilization), which greatly reduces the administrative burden for experimentation.
One impediment for the use of zebrafish in toxicity studies is the lack of standardized experimental protocols. Substantial variability has been observed among researchers in phenotypes reported from similar studies, as well as a lack of consistent data annotation, indicating a need for both terminological and data harmonization.
This led the NTP to create the SEAZIT initiative. SEAZIT is a multipronged, multiyear initiative to support generation of fundamental knowledge for the use of zebrafish in toxicology research and provide the scientific basis for NTP’s future use of zebrafish in chemical toxicity screening. Workshops and publications following the establishment of SEAZIT explored the use of ontologies as a tool for overcoming these data integration barriers.
Ontological knowledge structures can be leveraged to integrate diverse data sets across terminologies, scales, and modalities. To this purpose, zebrafish researchers were asked to assess images of zebrafish larvae for morphological malformations in two surveys. In the first survey, researchers were asked to annotate observed malformations using their own terminology. In the second survey, researchers were asked to annotate the images from a list of terms and definitions from the Zebrafish Phenotype Ontology. Analysis of the results suggested that the use of ontology terms increased consistency and decreased ambiguity, enabling comparison and data integration across laboratories.
We conclude that utilizing a common data standard will not only reduce the heterogeneity of reported terms, but increase agreement and repeatability between different laboratories. Thus, we advocate for the development of a zebrafish phenotype atlas to help laboratories create interoperable, computable data.