Modelling the liver’s regenerative capacity across different clinical conditions
Bibliographic record
Abstract
Background & Aims: Liver regeneration is essential for recovery following injury, but this process can be impaired by factors such as sex, age, metabolic disorders, fibrosis, and immunosuppressive therapies. We aimed to identify key transcriptomic, proteomic, and serum biomarkers of regeneration in mouse models under these diverse conditions using systems biology and machine learning approaches. Methods: Six mouse models, each undergoing 75% hepatectomy, were used to study regeneration across distinct clinical contexts: young males and females, aged mice, stage 2 fibrosis, steatosis, and tacrolimus exposure. A novel contrastive deep learning framework with triplet loss was developed to map regenerative trajectories and identify genes associated with regenerative efficiency. Results: . Proteomic validation and human SPLiT-seq (split-pool ligation-based transcriptome sequencing) data further supported their relevance across species. Conclusions: This study identifies conserved cell cycle regulators underlying efficient liver regeneration and provides a predictive framework for evaluating regenerative capacity. The integration of deep learning and multi-omics profiling provides a promising approach to better understand liver regeneration and may help guide therapeutic strategies, especially in complex clinical settings. Impact and implications: The aim of this study was to identify key transcriptomic, proteomic, and serum biomarkers of regeneration in mouse models under diverse conditions, using systems biology and machine learning approaches. Key molecular drivers of liver regeneration across diverse clinical conditions were identified using innovative deep learning and multi-omics approaches. By identifying conserved cell cycle genes predictive of regenerative outcomes, this study offers a powerful framework to assess and potentially enhance liver recovery in older patients, those with fibrosis or steatosis, and/or those under immunosuppression.
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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 | 0.000 |
| 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".