NOV 18, 2020 11:00 AM EST

Basic Concepts in Imaging-based High-Throughput Screening and High-Throughput Profiling Assay Development

  • Toxicologist, United States Environmental Protection Agency

      Dr. Harrill works as a cellular and molecular toxicologist with the US Environmental Protection Agency's Center for Computational Toxicology and Exposure. Dr. Harrill’s expertise is in vitro toxicology, specifically the application of next generation sequencing, high content imaging (HCI) and other complementary technologies for high-throughput chemical hazard screening, characterization and risk assessment. Dr. Harrill is currently a lead investigator for NCCT’s high-throughput transcriptomics and high-throughput phenotypic profiling hazard screening programs that focus on the use of broad-based high-content profiling assays for concentration-response screening of environmental chemicals in human-derived in vitro test systems. Dr. Harrill received his B.S. in Biochemistry from North Carolina State University and a Ph.D. in Toxicology for the University of North Carolina at Chapel Hill. Dr. Harrill’s graduate and postdoctoral training focused on the application of transcriptomic technologies for evaluating mechanisms of pesticide neurotoxicity and development of HCI-based high-/medium-throughput methods for in vitro developmental neurotoxicity screening. Dr. Harrill then served as a principal investigator at a non-profit research institute researching the role of ligand-activated nuclear receptors in tissue development and liver carcinogenesis using transcriptomic technologies as well as developing novel in vitro models for assessing chemical effects on hepatic stem/progenitor cells. Dr. Harrill also has experience from the private sector in conducting human health risk assessments using USEPA and state-level guidance as well as devising and managing rapid-phase environmental sampling, analysis and data interpretation programs during events involving the release of potentially hazardous chemicals.


    This session introduces basic concepts of imaging-based high-throughput screening (HTS) and high-throughput profiling assay development. Imaging-based HTS assays are designed to evaluate a discrete cellular process and produce a single, or small number of quantitative outputs. In contrast, imaging-based HTP assays measure dozens to thousands of features and provide highly multiplexed quantitative outputs.  Either type of approach may be used to evaluate the effects of chemicals or other perturbagens on cellular biology. Topics for this session include (but are not limited to) considerations for model selection, endpoint selection, imaging assay design, identification and use of positive control and reference treatments, methods for evaluating assay dynamic range and approaches for evaluating assay reproducibility. Examples of HCS assays for a variety of biological processes including nuclear receptor activation, oxidative stress, apoptosis, neurite outgrowth and others will be explored. In addition, this presentation will explore the basic concepts of machine learning classification in the context of HTP assays such as Cell Painting. Attendees will gain a basic foundational knowledge of guiding principles underlying the development of imaging-based HTS and HTP assays.  The views expressed in this presentation are those of the author and do not necessarily reflect USEPA policy.

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