Variability in cardiac electrophysiology: Using experimentally-calibrated populations of models to move beyond the single virtual physiological human paradigm
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Physiological variability manifests itself via differences in physiological function between individuals of the same species, and has crucial implications in disease progression and treatment. Despite its importance, physiological variability has traditionally been ignored in experimental and computational investigations due to averaging over samples from multiple individuals. Recently, modelling frameworks have been devised for studying mechanisms underlying physiological variability in cardiac electrophysiology and pro-arrhythmic risk under a variety of conditions and for several animal species as well as human. One such methodology exploits populations of cardiac cell models constrained with experimental data, or experimentally-calibrated populations of models. In this review, we outline the considerations behind constructing an experimentally-calibrated population of models and review the studies that have employed this approach to investigate variability in cardiac electrophysiology in physiological and pathological conditions, as well as under drug action. We also describe the methodology and compare it with alternative approaches for studying variability in cardiac electrophysiology, including cell-specific modelling approaches, sensitivity-analysis based methods, and populations-of-models frameworks that do not consider the experimental calibration step. We conclude with an outlook for the future, predicting the potential of new methodologies for patient-specific modelling extending beyond the single virtual physiological human paradigm.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 it