Altered m6A RNA methylation profiles in depression implicate the dysregulation of discrete cellular functions in males and females
Bibliographic record
Abstract
Adverse environmental stress represents a significant risk factor for major depressive disorder (MDD), often resulting in disrupted synaptic connectivity which is known to be partly regulated by epigenetic mechanisms. N 6 -methyladenosine (m6A), an epitranscriptomic modification, has emerged as a crucial regulator of activity-dependent gene regulation. In this study, we characterized m6A profiles in the ventromedial prefrontal cortex (vmPFC) of individuals with MDD. Using m6A sequencing, we identified a total of 30,279 high-confidence m6A peaks, exhibiting significant enrichment in genes related to neuronal and synaptic function. The m6A peaks between males and females with MDD that passed the significance threshold showed opposite m6A patterns, while the threshold-free m6A patterns were concordant. Distinct m6A profiles were found in MDD for each sex, with dysregulation associated with microtubule movement in males and neuronal projection in females. Our results suggest the potential roles of m6A as part of the dysregulated molecular network in MDD.
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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".