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Challenges and Opportunities in Enabling High-Throughput, Miniaturized High Content Screening

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High Content Screening

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1683))

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.

Author information

Authors and Affiliations

  1. Primary Pharmacology Group, Pfizer Inc.,Groton, CT, USA, Pfizer Inc., New Haven, CT, USA

    Debra Nickischer

  2. Global Data Strategies and Solutions, Bristol-Myers Squibb, Wallingford, CT, USA

    Lisa Elkin

  3. High Content Biology for Discovery IT, Bristol-Myers Squibb, Princeton, NJ, USA

    Normand Cloutier

  4. Biomolecular Screening, Forma Scientific, Watertown, MA, USA

    Jonathan O’Connell

  5. Discovery and Optimization, Bristol-Myers Squibb, Wallingford, CT, USA

    Martyn Banks

  6. Primary Pharmacology Group, Pfizer Inc., Groton, CT, USA

    Andrea Weston

Authors
  1. Debra Nickischer
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  2. Lisa Elkin
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  3. Normand Cloutier
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  4. Jonathan O’Connell
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  5. Martyn Banks
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  6. Andrea Weston
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Corresponding author

Correspondence to Debra Nickischer .

Editor information

Editors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Paul A. Johnston

  2. Bahama Bio, LLC, Bahama, North Carolina, USA

    Oscar J. Trask

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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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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7355-2

  • Online ISBN: 978-1-4939-7357-6

  • eBook Packages: Springer Protocols

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