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Updated: Jun 8, 2025
07:09
A Bioinformatics Pipeline for Investigating Molecular Evolution and Gene Expression using RNA-seq
Published on: May 28, 2021
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Bioinformatic workflows for deriving transcriptomic points of departure: current status, data gaps, and research
Jason O'Brien1, Constance Mitchell2, Scott Auerbach3
1Ecotoxicology and Wildlife Health Division, Environment and Climate Change Canada, Ottawa, ON J8X 4C6, Canada.
Summary
Transcriptomic points of departure (tPODs) offer a health-protective and efficient method for toxicological safety assessment. This approach uses gene expression data for faster, reliable chemical safety evaluations compared to traditional methods.
Area of Science:
- Toxicology and Molecular Biology
- Computational Biology and Bioinformatics
Background:
- Conventional toxicology relies on animal testing, which is time-consuming and costly.
- There is a growing need for efficient and reliable methods in toxicological safety assessment.
- Molecular data, particularly transcriptomics, offers a promising alternative for evaluating chemical safety.
Purpose of the Study:
- To review the current state of science for deriving transcriptomic points of departure (tPODs).
- To identify best practices, variability, data gaps, and uncertainties in tPOD generation.
- To provide recommendations for the adoption of tPODs in regulatory toxicology.
Main Methods:
- Review of study designs and bioinformatics workflows for tPOD derivation.
- Analysis of dose-response modeling for individual genes and aggregation of gene-level data.
- Evaluation of methodologies for generating tPODs from transcriptomic data.
Main Results:
- Transcriptomic analyses provide global molecular change snapshots reflecting cellular responses to stressors.
- tPODs identify dose levels below which gene expression changes are not expected.
- Reference doses derived using tPODs are supported by research as being health protective.
Conclusions:
- tPODs offer a faster and potentially more reliable approach to safety assessment than conventional methods.
- Rigorous and reproducible methodologies are essential for the regulatory application of tPODs.
- Further research is recommended to address barriers and promote the adoption of tPODs in regulatory decision-making.
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