Genetic network structure and dynamics: identifying simple negative feedback loops
Bibliographic record
Abstract
A broad array of experimental techniques have been used to determine the interactions between genes that regulate key cellular processes such as differentiation, metabolism and the cell cycle. The experimental studies are often complemented by development of models of varying degrees of complexity. We consider the ‘inverse problem’: to determine the underlying interactions based solely on the observed dynamics. In earlier work, we considered a specific class of ordinary differential equations that are continuous analogues of a Boolean switching network. We developed techniques to analyse and classify the dynamics based on their logical structure. We also developed techniques to solve the inverse problem. In the current work, we extend these earlier methods to analyse a model equation for a genetic network proposed by Cummins and colleagues. For a simple negative feedback system in which there is a cyclic interaction diagram with an odd number of inhibitory links, if the data is sampled at a sufficiently fine time scale with sufficient accuracy that maxima and minima can be determined, the structure can be deduced by considering sequences of maxima and minima. Alternatively, one can use the sequence of logical states found by discretizing the dynamics based on the first derivative of the variables as a function of time. The most useful technique for determining the interactions involves assessing the dependence of the rate of change of each variable as a function of the other variables, taken one at a time.
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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 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| 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".