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Development and Use of a High Content Imaging-Based Phenotypic Profiling Assay for Bioactivity Screening of Environmental Chemicals (SBI2)
Citation:
Nyffeler, J., C. Willis, AND J. Harrill. Development and Use of a High Content Imaging-Based Phenotypic Profiling Assay for Bioactivity Screening of Environmental Chemicals (SBI2). Society of Biomolecular Imaging and Informatics (SBI2) Conference, Boston, MA, September 17 - 19, 2019. https://doi.org/10.23645/epacomptox.11396865
Impact/Purpose:
Presentation to the Society of Biomolecular Imaging and Informatics (SBI2) Conference in September 2019 on some of the work being done by the EPA National Center for Computational Toxicology. NCCT research programs focus on developing the tools, approaches and data needed to accelerate the pace of chemical risk assessment and foster incorporation of non-traditional toxicity testing data into regulatory decision making processes. The NCCT research portfolio is divided into four major topic areas: 1) Chemical characterization, 2) Hazard Evaluation, 3) Toxicokinetics and & In Vitro Disposition and 4) Exposure Assessment. Information within each topic area is generated and integrated using a combination of high throughput screening and computational modeling approaches.
Description:
The EPA's National Center for Computational Toxicology research programs focus on developing the tools, approaches and data needed to accelerate the pace of chemical risk assessment and foster incorporation of non-traditional toxicity testing data into regulatory decision-making processes. In a new approach for hazard evaluation, we employ broad-based (i.e. non-targeted) profiling assays that cast the broadest net possible for capturing potential hazards associated with chemical treatment and may be used to group chemicals based on similarity in bioactivity profiles. We have adapted the Cell Painting assay and developed computational workflows for phenotypic feature extraction, data normalization, concentration-response modeling and generation of phenotypic response profiles. We also demonstrated reproducibility of potency estimates and phenotypic profiles in the Cell Painting assay using phenotypic reference chemicals. Using the bioactivity exposure ratio (BER), high-throughput phenotypic profiling (HTPP) data may be used in combination with In Vitro-in-In Vivo (IVIVE) and ExpoCast estimates to identify chemicals with bioactiity thresholds in human relevant exposure ranges. Utilizing chemical read across concepts, vector-based similarity approaches were able to identify structurally related chemicals with similar response profiles. The views expressed in this presentation are those of the presenters and do not necessarily reflect the views or policies of the US EPA.
URLs/Downloads:
DOI: Development and Use of a High Content Imaging-Based Phenotypic Profiling Assay for Bioactivity Screening of Environmental Chemicals (SBI2)
NYFFELER_2019-09-09_SBI2_2019_V1.PDF (PDF, NA pp, 8893.574 KB, about PDF)