Unraveling the characteristics of microRNA regulation in the developmental and aging process of the human brain
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Bibliographic record
Abstract
BACKGROUND: Structure and function of the human brain are subjected to dramatic changes during its development and aging. Studies have demonstrated that microRNAs (miRNAs) play an important role in the regulation of brain development and have a significant impact on brain aging and neurodegeneration. However, the underlining molecular mechanisms are not well understood. In general, development and aging are conventionally studied separately, which may not completely address the physiological mechanism over the entire lifespan. Thus, we study the regulatory effect between miRNAs and mRNAs in the developmental and aging process of the human brain by integrating miRNA and mRNA expression profiles throughout the lifetime. METHODS: In this study, we integrated miRNA and mRNA expression profiles in the human brain across lifespan from the network perspective. First, we chose the age-related miRNAs by polynomial regression models. Second, we constructed the bipartite miRNA-mRNA regulatory network by pair-wise correlation coefficient analysis between miRNA and mRNA expression profiles. At last, we constructed the miRNA-miRNA synergistic network from the miRNA-mRNA network, considering not only the enrichment of target genes but also GO function enrichment of co-regulated target genes. RESULTS: We found that the average degree of age-related miRNAs was significantly higher than that of non age-related miRNAs in the miRNA-mRNA regulatory network. The topological features between age-related and non age-related miRNAs were significantly different, and 34 reliable age-related miRNA synergistic modules were identified using Cfinder in the miRNA-miRNA synergistic network. The synergistic regulations of module genes were verified by reviewing miRNA target databases and previous studies. CONCLUSIONS: Age-related miRNAs play a more important role than non age-related mrRNAs in the developmental and aging process of the human brain. The age-related miRNAs have synergism, which tend to work together as small modules. These results may provide a new insight into the regulation of miRNAs in the developmental and aging process of the human brain.
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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) | 0.000 | 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 it