PUBLICATION
A versatile, automated and high-throughput drug screening platform for zebrafish embryos
- Authors
- Lubin, A., Otterstrom, J., Hoade, Y., Bjedov, I., Stead, E., Whelan, M., Gestri, G., Paran, Y., Payne, E.
- ID
- ZDB-PUB-210903-3
- Date
- 2021
- Source
- Biology Open 10(9): (Journal)
- Registered Authors
- Gestri, Gaia, Payne, Elspeth M. (Beth)
- Keywords
- Drug screening, High-throughput, Zebrafish
- MeSH Terms
-
- Algorithms
- Animals
- Drug Evaluation, Preclinical/methods*
- Embryo, Nonmammalian/drug effects*
- High-Throughput Screening Assays/methods*
- Models, Animal*
- Phenotype
- Zebrafish/embryology*
- PubMed
- 34472582 Full text @ Biol. Open
Citation
Lubin, A., Otterstrom, J., Hoade, Y., Bjedov, I., Stead, E., Whelan, M., Gestri, G., Paran, Y., Payne, E. (2021) A versatile, automated and high-throughput drug screening platform for zebrafish embryos. Biology Open. 10(9):.
Abstract
Zebrafish provide a unique opportunity for drug screening in living animals, with the fast-developing, transparent embryos allowing for relatively high-throughput, microscopy-based screens. However, the limited availability of rapid, flexible imaging and analysis platforms has limited the use of zebrafish in drug screens. We have developed an easy-to-use, customisable automated screening procedure suitable for high-throughput phenotype-based screens of live zebrafish. We utilised the WiScan® Hermes High Content Imaging System to rapidly acquire brightfield and fluorescent images of embryos, and the WiSoft® Athena Zebrafish Application for analysis, which harnesses an Artificial Intelligence-driven algorithm to automatically detect fish in brightfield images, identify anatomical structures, partition the animal into regions and exclusively select the desired side-oriented fish. Our initial validation combined structural analysis with fluorescence images to enumerate GFP-tagged haematopoietic stem and progenitor cells in the tails of embryos, which correlated with manual counts. We further validated this system to assess the effects of genetic mutations and X-ray irradiation in high content using a wide range of assays. Further, we performed simultaneous analysis of multiple cell types using dual fluorophores in high throughput. In summary, we demonstrate a broadly applicable and rapidly customisable platform for high-content screening in zebrafish. This article has an associated First Person interview with the first author of the paper.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping