(1016-A) A strategy for comparing in vitro ‘omic technologies to existing rat in vivo data
Monday, February 5, 2024
12:00 PM – 1:00 PM EST
Location: Exhibit Halls AB
Abstract: Author List: Srijit Seal, on behalf of the OASIS Consortium
Abstract: There is an urgent need for more efficient, translational, and less animal-reliant testing strategies that ensure the safety of pharmaceutical and agrochemical products. Responding to this demand, a diverse consortium of experts from industry, government, academia, and research institutes has been convened. The ‘Omics for Assessing Signatures for Integrated Safety (OASIS) Consortium has initiated the design and implementation of a pioneering experimental study to advance the integration of in vitro 'omics approaches into safety evaluation. The OASIS study aims to produce novel data using Cell Painting (high-throughput image-based profiling), transcriptomics, and proteomics for over 1500 data-rich compounds associated with liver toxicity, tested at 8 concentrations each. High-dimensional ‘omics profiles of various types (cell morphology, gene expression, protein expression) will be generated in human U2OS cells, HepaRG cells, and rat primary hepatocytes and may involve advanced models (liver organoids; liver-on-a-chip. This study will be the first to use bioinformatic methods to integrate cell painting, transcriptomics, and proteomics data, and derive in vitro points of departure (PODs) across these ‘omics technologies. These novel in vitro PODs are of potential value to chemical safety assessment and will be further compared with existing in vivo liver toxicity data (organ weight, clinical pathology, and histopathology data). The comparison of these novel in vitro methods with existing in vivo datasets will advance our understanding of their translational utility and their potential for broader integration in a new approach methodology (NAM)s-driven approach.