Circadian oscillations of cytosine modification in humans contribute to epigenetic variability, aging, and complex disease
Bibliographic record
Abstract
BACKGROUND: Maintenance of physiological circadian rhythm plays a crucial role in human health. Numerous studies have shown that disruption of circadian rhythm may increase risk for malignant, psychiatric, metabolic, and other diseases. RESULTS: Extending our recent findings of oscillating cytosine modifications (osc-modCs) in mice, in this study, we show that osc-modCs are also prevalent in human neutrophils. Osc-modCs may play a role in gene regulation, can explain parts of intra- and inter-individual epigenetic variation, and are signatures of aging. Finally, we show that osc-modCs are linked to three complex diseases and provide a new interpretation of cross-sectional epigenome-wide association studies. CONCLUSIONS: Our findings suggest that loss of balance between cytosine methylation and demethylation during the circadian cycle can be a potential mechanism for complex disease. Additional experiments, however, are required to investigate the possible involvement of confounding effects, such as hidden cellular heterogeneity. Circadian rhythmicity, one of the key adaptations of life forms on Earth, may contribute to frailty later in life.
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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".