Robust oscillations in multi-cyclic Markov state models of biochemical clocks
Bibliographic record
Abstract
Organisms often use cyclic changes in the concentrations of chemical species to precisely time biological functions. Underlying these biochemical clocks are chemical reactions and transport processes, which are inherently stochastic. Understanding the physical basis for robust biochemical oscillations in the presence of fluctuations has thus emerged as an important problem. In a previous paper [C. del Junco and S. Vaikuntanathan, Phys. Rev. E 101, 012410 (2020)], we explored this question using the non-equilibrium statistical mechanics of single-ring Markov state models of biochemical networks that support oscillations. Our finding was that they can exploit non-equilibrium driving to robustly maintain the period and coherence of oscillations in the presence of randomness in the rates. Here, we extend our work to Markov state models consisting of a large cycle decorated with multiple small cycles. These additional cycles are intended to represent alternate pathways that the oscillator may take as it fluctuates about its average path. Combining a mapping to single-cycle networks based on first passage time distributions with our previously developed theory, we are able to make analytical predictions for the period and coherence of oscillations in these networks. One implication of our predictions is that a high energy budget can make different network topologies and arrangements of rates degenerate as far as the period and coherence of oscillations are concerned. Excellent agreement between analytical and numerical results confirms that this is the case. Our results suggest that biochemical oscillators can be more robust to fluctuations in the path of the oscillator when they have a high energy budget.
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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 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".