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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Autores principales: Alexandra Lubin, Jason Otterstrom, Yvette Hoade, Ivana Bjedov, Eleanor Stead, Matthew Whelan, Gaia Gestri, Yael Paran, Elspeth Payne
Formato: article
Lenguaje:EN
Publicado: The Company of Biologists 2021
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Acceso en línea:https://doaj.org/article/dbe9a58d3e134c6e8b6b6f9413ca06f5
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic drug screening
high-throughput
zebrafish
Science
Q
Biology (General)
QH301-705.5
spellingShingle 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
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