High-Throughput Transcriptomic Profiling for Bioactivity Screening: Mapping Molecular Targets and Potencies for Tox21 chemicals in HepaRG Cells

The chemical set was selected to span a broad range of known molecular targets and biological response pathways. Cells were exposed to each chemical in a 7-point concentration-response format (0.1?100 µM) for 24 hours, and transcriptomic changes were measured using the TempO-Seq human whole transcriptome version 2 (hWTv2) assay (~20,000 genes).

The objective of this study was to develop a compendium of transcriptional profiles from mechanistically annotated reference chemicals to support interpretation of HTTr data from uncharacterized compounds. These profiles enable identification of gene expression signatures associated with specific molecular targets and pathways, and allow evaluation of concentration-dependent activation patterns across pathways. This dataset provides a foundation for linking chemical exposures to biological mechanisms, informing hazard characterization, and supporting predictive toxicology.