Efficiency-fluctuation trade-offs in biomolecular assembly processes
Bibliographic record
Abstract
Stochastic fluctuations of molecular abundances are a ubiquitous feature of cellular processes and lead to significant cell-to-cell variability even in clonal populations under identical conditions. Recent theoretical work established lower bounds for stochastic fluctuations in cells for broad classes of cellular processes by analyzing the dynamics of reaction motifs that are embedded within a larger network with arbitrary interactions and dynamics. For example, a class of generalized assembly processes in which two co-regulated subunits irreversibly form a complex was shown to exhibit an unavoidable trade-off between assembly efficiency and subunit fluctuations: Regardless of rate constants and details of feedback control, subunit fluctuations were shown to diverge as the assembly efficiency approaches 100%. In contrast, other work has reported how efficient assembly processes work as stochastic noise filters or can achieve robust adaptation through integral control. While all of these results are technically correct their seemingly contradictory conclusions raise the question of how broadly applicable the previously reported efficiency-fluctuation trade-off is. Here, we show that a much broader class of assembly processes than previously considered is subject to an efficiency-fluctuation trade-off which diverges in the high efficiency regime. We find the proposed noise filtering property of efficient assembly processes corresponds to a singular limit of this class of systems. Additionally, we show that combining feedback control with distinct subunit synthesis rates is a necessary condition to overcome the generalized efficiency-fluctuation trade-off. Through numerical examples, we show that biomolecular integral controllers are one of several realizations of such control. How small a change to joint subunit control is sufficient to avoid diverging fluctuations in the high-efficiency limit remains an open question.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".