Using random perturbations to infer the structure of feedback control in gene expression
Bibliographic record
Abstract
Feedback in cellular processes is typically inferred through cellular responses to experimental perturbations. Modular response analysis provides a theoretical framework for translating specific perturbations into feedback sensitivities between cellular modules. However, in large-scale drug perturbation studies the effect of any given drug may not be known and may not only affect one module at a time. Here, we analyze the response of gene expression models to random perturbations that affect multiple modules simultaneously. In the deterministic regime we analytically show how cellular responses to infinitesimal random perturbations can be used to infer the nature of feedback regulation in gene expression, as long as the effects of perturbations are statistically independent between modules. We numerically extend this deterministic analysis to the response of average abundances of stochastic gene expression models to finite perturbations. Across a large sample of stochastic models, the response of average abundances generally obeyed predicted bounds from the deterministic analysis, but dramatic deviations occurred in systems with bimodal or fat-tailed stationary state distributions. These discrepancies demonstrate how deterministic analyses can fail to capture the effect of perturbations on averages of stochastic cellular feedback systems--even in the linear response regime.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 | 0.009 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".