Abstract
Within the Drug Discovery industry, there is a growing recognition of the value of high content screening (HCS), particularly as researchers aim to screen compounds and identify hits using more physiologically relevant in vitro cell-based assays. Image-based high content screening, with its combined ability to yield multiparametric data, provide subcellular resolution, and enable cell population analysis, is well suited to this challenge. While HCS has been in routine use for over a decade, a number of hurdles have historically prohibited very large, miniaturized high-throughput screening efforts with this platform. Suitable hardware and consumables for conducting 1536-well HCS have only recently become available, and developing a reliable informatics framework to accommodate the scale of high-throughput HCS data remains a considerable challenge. Additionally, innovative approaches are needed to interpret the large volumes of content-rich information generated. Despite these hurdles, there has been a growing interest in screening large compound inventories using this platform. Here, we outline the infrastructure developed and applied at Bristol-Myers Squibb for 1536-well high content screening and discuss key lessons learned.
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Acknowledgments
The authors wish to thank members of the Core Automation team including Jennifer Zewinski, Jeffrey Cheicko, Lisa Simoni, David Connors, Christian Ferrante and Jessica Devito for providing critical support in enabling high-throughput HCS assays. Additionally, we acknowledge the efforts of Michael Lenard and Donald Jackson in the development and implementation of HCS Road, as well as informatics support to enable phenotypic clustering. Judi Wardwell-Swanson and Yanhua Hu were instrumental in the development and execution of the phenotypic clustering methods described. Finally, thanks are due to Edward Pineda for providing us with the CADD drawings in Fig. 3.
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Nickischer, D., Elkin, L., Cloutier, N., O’Connell, J., Banks, M., Weston, A. (2018). Challenges and Opportunities in Enabling High-Throughput, Miniaturized High Content Screening. In: Johnston, P., Trask, O. (eds) High Content Screening. Methods in Molecular Biology, vol 1683. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7357-6_11
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DOI: https://doi.org/10.1007/978-1-4939-7357-6_11
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