Bioinformatic Workflows for Deriving Transcriptomic Points of Departure: Current status, Data Gaps, and Research Priorities

This comprehensive review, from HESI's Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee, explores the use of transcriptomic points of departure (tPODs) to enhance toxicological safety assessment. The article delves into current methodologies for deriving tPODs from transcriptomic data, identifying sources of variability, key gaps in knowledge, and areas for future research. It highlights the potential of tPODs to deliver faster and health-protective toxicological assessments compared to traditional methods.

Key Takeaways:

• Efficiency and Innovation: tPODs offer a novel approach to derive reference doses using short-term studies, reducing reliance on long-term animal testing.
• Bioinformatic Workflows: The review provides a detailed nine-step framework for tPOD derivation, including data processing, normalization, and response detection.
• Research Priorities: Critical areas for improvement include study design optimization, platform standardization, and enhanced methods for uncertainty quantification.
• Regulatory Relevance: The findings emphasize the integration of tPODs into regulatory toxicology, supported by robust bioinformatic tools like EPA’s ETAP and BMDExpress.

This article is a must-read for:

• Toxicologists and Risk Assessors seeking advanced methodologies for safety assessments.
• Bioinformaticians interested in data workflows and transcriptomics.
• Academics and Industry Professionals involved in molecular toxicology research.

The full article is open access and can be read at the link below.

Bioinformatic Workflows for Deriving Transcriptomic Points of Departure: Current status, Data Gaps, and Research Priorities
O’Brien et al., Toxicological Sciences, https://doi.org/10.1093/toxsci/kfae145