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High Throughput Phenotypic Profiling of ToxCast Chemicals Using Cell Painting
Citation:
Harrill, J. High Throughput Phenotypic Profiling of ToxCast Chemicals Using Cell Painting. Springer Nature Webinar, NA, North Carolina, October 21, 2020. https://doi.org/10.23645/epacomptox.13370120
Impact/Purpose:
The US EPA Center for Computational Toxicology and Exposure has research programs focused 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. High-throughput phenotypic profiling (HTPP) with Cell Painting is a promising technology for comprehensive and cost-effective bioactivity screening of chemicals. We have developed robust laboratory and bioinformatics workflows for generating HTPP data on thousands of chemicals in concentration-response. Information gleaned from this assay includes molecular point of departures representing the threshold for perturbation of cellular biology and phenotypic profiles that can be used to identify chemicals that act through similar mechanisms of action. This information would be of interest to scientists using or contemplating the use of new approach methodologies (NAMs) for next generation risk assessment (NGRA).
Description:
This submission is slides for a webinar hosted by Springer Nature. The number of chemicals in the environment that originate from anthropogenic sources is immense. Regulatory scientists are faced with the challenge of efficiently and credibility evaluating the safety of chemicals found in the environment, often with limited or no available toxicity data to guide them. Traditional toxicity testing strategies involving the use of laboratory animals are inefficient, expensive and in some cases limited in terms of predicting human health effects. In recent years there has been a movement in the regulatory sciences to replace, reduce and refine the use of laboratory animals in toxicity testing and bring to bear advances in biotechnology and bioinformatics to address the “too many chemicals, too little data” challenge. In this webcast, the speaker will the discuss the use of an “in vitro pathology” assay known as Cell Painting for bioactivity profiling of environmental chemicals from the US EPA ToxCast collection. Information gleaned from this assay includes molecular point-of-departures (PODs) based on threshold concentrations for perturbation of cellular biology and phenotypic profiles that can be used to identify chemicals that may be acting through similar mechanisms of action. The speaker will demonstrate how this information can be used to inform next generation chemical safety assessments. This abstract does not reflect USEPA policy. You will learn about: • The use of Cell Painting for bioactivity screening of chemicals found in the environment. • Computational approaches for concentration-response modeling of high-dimensional profiling data. • Practical applications of high-throughput profiling data for chemical safety assessment.
URLs/Downloads:
DOI: High Throughput Phenotypic Profiling of ToxCast Chemicals Using Cell Painting
HARRILL_NATURE_HTPP_V3.PDF (PDF, NA pp, 11894.101 KB, about PDF)