Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Search research articles

Related Experiment Video

Updated: May 9, 2025

Gene Expression Profiling of Infecting Microbes Using a Digital Bar-coding Platform

Gene Expression Profiling of Infecting Microbes Using a Digital Bar-coding Platform

Published on: January 13, 2016

Incorporating Metabolic Competence into High-Throughput Profiling Assays.

Amanda Jurgelewicz^1,2, Kristen Breaux¹, Clinton M Willis¹

¹Center for Computational Toxicology and Exposure (CCTE), Office of Research and Development (ORD), US Environmental Protection Agency, Durham, NC 27709, United States.

Toxicological Sciences : an Official Journal of the Society of Toxicology

|May 3, 2025

Summary

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

A high-throughput chemotaxis assay for assessing immunotoxicity using multiple human immune cell types.

NAM journal·2026

Same author

Characterizing Accuracy of Model Predictions for Chemical Concentration in High Throughput Screening Assays.

Environmental science & technology·2026

Same author

Interlaboratory validation of the human thyroid microtissue assay.

Toxicological sciences : an official journal of the Society of Toxicology·2025

Same author

Bridging in vitro and in vivo inhalation toxicity: Volatile organic compounds elicit similar transcriptomic points of departure in human airway cells and mouse respiratory tract.

Environmental pollution (Barking, Essex : 1987)·2025

Same author

Cell painting in HepaRG cells: an interlaboratory reproducibility study.

Toxicological sciences : an official journal of the Society of Toxicology·2025

Same author

Phenotypic Profiling of 6PPD, 6PPD-quinone and Structurally Diverse Antiozonants in RTgill-W1 Cells Using the Cell Painting Assay.

Environmental science & technology letters·2025

This summary is machine-generated.

This study integrated metabolic enzymes into high-throughput chemical screening assays, revealing that metabolism significantly alters chemical bioactivity and estrogen receptor activation. This approach enhances chemical risk assessment by detecting metabolite-specific effects.

Area of Science:

Toxicology
Chemical Biology
Drug Metabolism

Background:

High-throughput screening (HTS) assays like Cell Painting (HTPP) and TempO-Seq (HTTr) characterize chemical bioactivity and hazards.
Current in vitro HTS assays lack human or animal metabolic capabilities, limiting their predictive power for in vivo effects.
Assessing chemical metabolites is crucial for accurate risk assessment.

Purpose of the Study:

To evaluate the impact of chemical metabolism on bioactivity using HTS assays.
To integrate the Alginate Immobilization of Metabolic Enzymes (AIME) platform with HTPP and HTTr assays.
To assess chemical bioactivity changes in a breast cancer cell line (VM7Luc4E2) with and without metabolic capacity.

Main Methods:

Coupled the AIME platform with Cell Painting (HTPP) and TempO-Seq (HTTr) assays.

Keywords:

cell painting estrogen receptor high-throughput phenotypic profiling high-throughput transcriptomics new approach methods xenobiotic metabolism

More Related Videos

High-Throughput Metabolic Profiling for Model Refinements of Microalgae

High-Throughput Metabolic Profiling for Model Refinements of Microalgae

Published on: December 4, 2021

Author Spotlight: Cost-Effective Transcriptomic Drug Screening - Unlocking New Targets

Author Spotlight: Cost-Effective Transcriptomic Drug Screening - Unlocking New Targets

Published on: February 23, 2024

Related Experiment Videos

Last Updated: May 9, 2025

Gene Expression Profiling of Infecting Microbes Using a Digital Bar-coding Platform

Gene Expression Profiling of Infecting Microbes Using a Digital Bar-coding Platform

Published on: January 13, 2016

High-Throughput Metabolic Profiling for Model Refinements of Microalgae

High-Throughput Metabolic Profiling for Model Refinements of Microalgae

Published on: December 4, 2021

Author Spotlight: Cost-Effective Transcriptomic Drug Screening - Unlocking New Targets

Author Spotlight: Cost-Effective Transcriptomic Drug Screening - Unlocking New Targets

Published on: February 23, 2024

Utilized an estrogen receptor transactivation assay (ERTA) to measure ER activation.

Exposed VM7Luc4E2 cells to chemicals with and without the AIME-generated metabolites.

Main Results:

HTPP demonstrated concentration-dependent increases in bioactivity linked to enhanced estrogen receptor (ER) activation.
HTTr detected more active genes under metabolic conditions, correlating with increased ER activation.
Metabolism-induced shifts in ER high-confidence (ERHC) gene signature enrichment were observed, serving as a transcriptomic readout for ER activity.

Conclusions:

The AIME platform successfully integrated with HTPP and HTTr assays to detect reproducible changes in chemical bioactivity due to metabolism.
Incorporating metabolic competence into HTS assays improves the characterization of chemical hazards.
This approach enhances next-generation risk assessment by identifying metabolite-specific bioactivity missed by current screening methods.