REPA: Applying Pathway Analysis to Genome-Wide Transcription Factor Binding Data
Bibliographic record
Abstract
Pathway analysis has been extensively applied to aid in the interpretation of the results of genome-wide transcription profiling studies, and has been shown to successfully find associations between the biological phenomena under study and biological pathways. There are two widely used approaches of pathway analysis: over-representation analysis, and gene set analysis. Recently genome-wide transcription factor binding data has become widely available allowing for the application of pathway analysis to this type of data. In this work, we developed regulatory enrichment pathway analysis (REPA) to apply gene set analysis to genome-wide transcription factor binding data to infer associations between transcription factors and biological pathways. We used the transcription factor binding data generated by the ENCODE project, and gene sets from the Molecular Signatures and KEGG databases. Our results showed that 54 percent of the predictions examined have literature support and that REPA's recall is roughly 54 percent. This level of precision is promising as several of REPA's predictions are expected to be novel and can be used to guide new research avenues. In addition, the results of our case studies showed that REPA enhances the interpretation of genome-wide transcription profiling studies by suggesting putative regulators behind the observed transcriptional responses.
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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 | 0.005 | 0.015 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.008 | 0.004 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".