A High-Content RNAi Screen Identifies Ubiquitin Modifiers That Regulate TNF-Dependent Nuclear Accumulation of NF-κB
Bibliographic record
Abstract
The mammalian tumor necrosis factor (TNF) cytokine is a central mediator of inflammatory events. Recent studies revealed a number of complex and sophisticated interactions between the TNF pathway and the enzymatic activities encoded by ubiquitin ligases and deubiquitylation enzymes. However, very little is known about the identity of the ubiquitin pathway members that control the extent of ubiquitylation in TNF responses. To address this deficit, we conducted an unbiased, high-content screen of the human ubiquitin pathway for gene products that control defining features of the cellular response to TNF. In particular, we sought to identify ubiquitin modifying enzymes that alter the ability of TNF to regulate the nuclear accumulation of nuclear factor kappa B. In this screen, we identified and validated several novel regulators of the TNF pathway. We believe these regulators constitute potential targets for pharmacological interventions that manipulate TNF-dependent inflammation.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".