Peer Review #3 of "T1000: a reduced gene set prioritized for toxicogenomic studies (v0.1)"
Bibliographic record
Abstract
There is growing interest within regulatory agencies and toxicological research communities to develop, test, and apply new approaches, such as toxicogenomics, to more efficiently evaluate chemical hazards.Given the complexity of analyzing thousands of genes simultaneously, there is a need to identify reduced gene sets.Though several gene sets have been defined for toxicological applications, few of these were purposefully derived using toxicogenomics data.Here, we developed and applied a systematic approach to identify 1000 genes (called Toxicogenomics-1000 or T1000) highly responsive to chemical exposures.First, a co-expression network of 11,210 genes was built by leveraging microarray data from the Open TG-GATEs program.This network was then reweighted based on prior knowledge of their biological (KEGG, MSigDB) and toxicological (CTD) relevance.Finally, weighted correlation network analysis was applied to identify 258 gene clusters.T1000 was defined by selecting genes from each cluster that were most associated with outcome measures.For model evaluation, we compared the performance of T1000 to that of other gene sets (L1000, S1500, Genes selected by Limma, and random set) using two external datasets based on the rat model.Additionally, a smaller (T384) and a larger version (T1500) of T1000 were used for dose-response modeling to test the effect of gene set size.Our findings demonstrated that the T1000 gene set is predictive of apical outcomes across a range of conditions (e.g., in vitro and in vivo, dose-response, multiple species, tissues, and chemicals), and generally performs as well, or better than other gene sets available.
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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 | 0.012 | 0.073 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.006 | 0.004 |
| Science and technology studies | 0.004 | 0.001 |
| Scholarly communication | 0.008 | 0.004 |
| Open science | 0.004 | 0.006 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.375 | 0.196 |
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".