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Open AccessArticle

A Smart Imaging Workflow for Organ-Specific Screening in a Cystic Kidney Zebrafish Disease Model

Acquifer is a division of Ditabis, Digital Biomedical Imaging Systems AG, 75179 Pforzheim, Germany
Department of Pediatrics I, University Children’s Hospital Heidelberg, 69120 Heidelberg, Germany
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(6), 1290;
Received: 29 January 2019 / Revised: 25 February 2019 / Accepted: 10 March 2019 / Published: 14 March 2019
(This article belongs to the Special Issue Zebrafish 2.0: A Model for Toxicological Research)
The zebrafish is being increasingly used in biomedical research and drug discovery to conduct large-scale compound screening. However, there is a lack of accessible methodologies to enable automated imaging and scoring of tissue-specific phenotypes at enhanced resolution. Here, we present the development of an automated imaging pipeline to identify chemical modifiers of glomerular cyst formation in a zebrafish model for human cystic kidney disease. Morpholino-mediated knockdown of intraflagellar transport protein Ift172 in Tg(wt1b:EGFP) embryos was used to induce large glomerular cysts representing a robustly scorable phenotypic readout. Compound-treated embryos were consistently aligned within the cavities of agarose-filled microplates. By interfacing feature detection algorithms with automated microscopy, a smart imaging workflow for detection, centring and zooming in on regions of interests was established, which enabled the automated capturing of standardised higher resolution datasets of pronephric areas. High-content screening datasets were processed and analysed using custom-developed heuristic algorithms implemented in common open-source image analysis software. The workflow enables highly efficient profiling of entire compound libraries and scoring of kidney-specific morphological phenotypes in thousands of zebrafish embryos. The demonstrated toolset covers all the aspects of a complex whole organism screening assay and can be adapted to other organs, specimens or applications. View Full-Text
Keywords: zebrafish; high-content screening; automated imaging; image analysis zebrafish; high-content screening; automated imaging; image analysis
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Pandey, G.; Westhoff, J.H.; Schaefer, F.; Gehrig, J. A Smart Imaging Workflow for Organ-Specific Screening in a Cystic Kidney Zebrafish Disease Model. Int. J. Mol. Sci. 2019, 20, 1290.

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