DENetwork unveils non-differentially expressed genes with functional relevance across conditions through information flow perturbation
Bibliographic record
Abstract
Differential gene expression (DE) analysis of RNA-sequencing (RNA-seq) data is a standard approach for identifying phenotypic differences between conditions. However, traditional DE methods such as DESeq2 focus on expression changes alone, often overlooking non-differentially expressed (non-DE) genes that may play key regulatory roles. This limits their ability to identify upstream drivers of transcriptomic variation. To address this gap, we introduce DENetwork, a network-based approach that prioritizes genes based on their influence on global information flow. Each gene is scored using an in silico knockout strategy that quantifies its impact across the inferred gene network, capturing both DE and non-DE genes with potential functional relevance. DENetwork deciphers intricate regulatory and signaling networks driving transcriptomic variations between conditions with distinct phenotypes. Across simulated and disease-relevant RNA-seq datasets, DENetwork identifies non-DE regulators enriched in known pathways and phenotypic associations, providing mechanistic insights missed by standard DE analysis, with implications for target discovery and intervention.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".