BROAD-SCALE, MULTI-SYSTEM DYSREGULATION OF GENE EXPRESSION: TOWARD CLINICAL QUANTIFICATION OF AGING
Bibliographic record
Abstract
Our previous work on clinical blood biomarkers established statistical distance as a proxy for dysregulation from homeostatic norms. Here, we expand this approach to gene expression data, permitting the definition of many more systems at a finer biological scale. We conducted secondary data analysis with 880 whole-blood gene expression profiles from the Rotterdam Study. Systems were defined using Gene Ontology annotations. For each system, we calculated the correlation between Mahalanobis distance and age. Among 13,189 systems tested, 1029 showed evidence of age-related increases in dysregulation, substantially more than the 660 expected by chance. Furthermore, these systems were highly clustered, with a strong representation of systems related to immune cell function, renal function, protein localization and maintenance of proteostasis, ribosomal RNA metabolism and regulation of signaling pathways, such as the MAP kinase pathway or cell cycle phase transition pathways. These results imply the potential to develop fine-scale metrics of aging for clinical use.
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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 | 0.010 | 0.016 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 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".