Consensus findings of an International Workshops on Genotoxicity Testing Workshop on using Transcriptomic biomarkers to predict genotoxicity
Bibliographic record
Abstract
Gene expression biomarkers have the potential to identify genotoxic and nongenotoxic carcinogens, providing opportunities for integrated testing and reducing animal use. In August 2022, an International Workshops on Genotoxicity Testing (IWGT) workshop was held to critically review current methods to identify genotoxicants using transcriptomic profiling. Here, we summarize the workgroup’s findings on the state of the science regarding the use of transcriptomic biomarkers to identify genotoxic chemicals in vitro and in vivo. A total of 1341 papers were examined to identify the biomarkers that show the most promise for identifying genotoxicants. This revealed two independently derived in vivo biomarkers and three in vitro biomarkers that, when used in conjunction with standard computational techniques, can identify genotoxic chemicals in vivo (rat or mouse liver) or in human cells in culture using different gene expression profiling platforms, with predictive accuracies of ≥ 92%. These biomarkers have been validated to differing degrees, but typically show high reproducibility across transcriptomic platforms and model systems. They offer several advantages for applications in different contexts of use in genotoxicity testing including: early signal detection, moderate to high-throughput screening capacity, adaptability to different cell types and tissues, and insights on mechanistic information on DNA-damage response. Workshop participants agreed on consensus statements to advance the regulatory adoption of transcriptomic biomarkers for genotoxicity. The participants agreed that transcriptomic biomarkers have the potential to be used in conjunction with other biomarkers in integrated test strategies in vitro and using short-term rodent exposures to identify genotoxic and nongenotoxic chemicals that may……………….
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.095 | 0.068 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.005 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.005 | 0.004 |
| Scholarly communication | 0.008 | 0.006 |
| Open science | 0.006 | 0.019 |
| Research integrity | 0.015 | 0.024 |
| Insufficient payload (model declined to judge) | 0.010 | 0.006 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".