Chairs: Rita Ortega-Vallbona & Luiz Ladeira
The application of toxicogenomic data for safety assessment and decision-making is seen as a key underpinning of NAM-based technology, supporting the implementation of NGRA frameworks due to its speed and broad screening capacity. It has been used to characterise dose-dependent changes in vitro gene to generate points of departure, aid understanding of toxicological effects and has also been used with defined approaches for hazard identification. Despite these advances, several challenges have hindered its widespread acceptance as a tool within the risk assessment community. Including difficulties understanding the data within current assessment frameworks, the complexity of transcriptomic data, as well as concerns around reproducibility and sensitivity. In a recent publication, Johnson et al 2023 identified 4 key principles that need to be met to drive future acceptance of transcriptomics in risk assessment
In this session, we address these challenges and provide updates on where current advances and capabilities in high-throughput transcriptomics are in relation to these principles to build confidence in the interpretation of the data generated for integration into regulatory practices. The initial presentations explore methods for evaluating signal and noise in data, addressing false positive rates and the absence of a defined ground truth. Additionally, we examine biological coverage and variability in responses within human cell lines. We further highlight developments in the comparison and impact of HTTr technologies, looking at the reproducibility of the data, as well as the development of open source tools to provide transparency and reduce the need for complex bioinformatics resources. The next talk elaborates on the development of TXG-MAPr to enhance mechanistic interpretation and increase the mapped biological space. Finally, the session will close by providing a view from a regulatory perspective on needs and requirements to enable the use and interpretation of HTTr data for decision-making.
Speakers
- Rayane Boufalaas – Inhalation Permeability Assessment using combined in vitro & in silico approaches
- Eike Cöllen – Establishment of an in-vitro neurotoxicity test battery using 2D/3D neuronal cell models for the assessment of functional disturbances in the nervous system
- Mahshid Alimohammadi – A generalizable approach to establish neurotoxicity assays with heightened sensitivity for mitochondrial toxicants
- Lucy Sinke – Enhancing mechanism-based neurotoxicity evaluations with in vitro LUHMES-based gene co-expression network analysis
- Matthias Wehr – Threshold of Toxicological Concern (TTC) and new opportunities in the era of AI
- Karolina Kopanska – ONTOX Probabilistic Risk Assessment (OPRA): An AI-enabled framework