Constructing kinetic models of metabolism at genome‐scales: A review
Bibliographic record
Abstract
Constraint-based modeling of biological networks (metabolism, transcription and signal transduction), although used successfully in many applications, suffer from specific limitations such as the lack of representation of metabolite concentrations and enzymatic regulation, which are necessary for a complete physiologically relevant model. Kinetic models conversely overcome these shortcomings and enable dynamic analysis of biological systems for enhanced in silico hypothesis generation. Nonetheless, kinetic models also have limitations for modeling at genome-scales chiefly due to: (i) model non-linearity; (ii) computational tractability; (iii) parameter identifiability; (iv) estimability; and (v) uncertainty. In order to support further development of kinetic models as viable alternatives to constraint-based models, this review presents a brief description of the existing obstacles towards building genome-scale kinetic models. Specific kinetic modeling frameworks capable of overcoming these obstacles are covered in this review. The tractability and physiological feasibility of these models are discussed with the objective of using available in vivo experimental observations to define the model parameter space. Among the different methods discussed, Monte Carlo kinetic models of metabolism stand out as potentially tractable methods to model genome scale networks while also addressing in vivo parameter uncertainty.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".