A versatile, automated and high-throughput drug screening platform for zebrafish embryos
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 zeb...
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The Company of Biologists
2021
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oai:doaj.org-article:dbe9a58d3e134c6e8b6b6f9413ca06f52021-11-28T16:01:06ZA versatile, automated and high-throughput drug screening platform for zebrafish embryos2046-639010.1242/bio.058513https://doaj.org/article/dbe9a58d3e134c6e8b6b6f9413ca06f52021-09-01T00:00:00Zhttp://bio.biologists.org/content/10/9/bio058513https://doaj.org/toc/2046-6390Zebrafish 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.Alexandra LubinJason OtterstromYvette HoadeIvana BjedovEleanor SteadMatthew WhelanGaia GestriYael ParanElspeth PayneThe Company of Biologistsarticledrug screeninghigh-throughputzebrafishScienceQBiology (General)QH301-705.5ENBiology Open, Vol 10, Iss 9 (2021) |
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drug screening high-throughput zebrafish Science Q Biology (General) QH301-705.5 |
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drug screening high-throughput zebrafish Science Q Biology (General) QH301-705.5 Alexandra Lubin Jason Otterstrom Yvette Hoade Ivana Bjedov Eleanor Stead Matthew Whelan Gaia Gestri Yael Paran Elspeth Payne A versatile, automated and high-throughput drug screening platform for zebrafish embryos |
description |
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. |
format |
article |
author |
Alexandra Lubin Jason Otterstrom Yvette Hoade Ivana Bjedov Eleanor Stead Matthew Whelan Gaia Gestri Yael Paran Elspeth Payne |
author_facet |
Alexandra Lubin Jason Otterstrom Yvette Hoade Ivana Bjedov Eleanor Stead Matthew Whelan Gaia Gestri Yael Paran Elspeth Payne |
author_sort |
Alexandra Lubin |
title |
A versatile, automated and high-throughput drug screening platform for zebrafish embryos |
title_short |
A versatile, automated and high-throughput drug screening platform for zebrafish embryos |
title_full |
A versatile, automated and high-throughput drug screening platform for zebrafish embryos |
title_fullStr |
A versatile, automated and high-throughput drug screening platform for zebrafish embryos |
title_full_unstemmed |
A versatile, automated and high-throughput drug screening platform for zebrafish embryos |
title_sort |
versatile, automated and high-throughput drug screening platform for zebrafish embryos |
publisher |
The Company of Biologists |
publishDate |
2021 |
url |
https://doaj.org/article/dbe9a58d3e134c6e8b6b6f9413ca06f5 |
work_keys_str_mv |
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