Hybrid representation learning for human m6A modifications with chromosome-level generalizability
Why this work is in the frame
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Bibliographic record
Abstract
Abstract Motivation N 6 - methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA and plays essential roles in post-transcriptional gene regulation. While several deep learning approaches have been proposed to predict m6A sites, most suffer from limited chromosome-level generalizability due to evaluation on randomly split datasets. Results In this study, we propose two novel hybrid deep learning models—Hybrid Model and Hybrid Deep Model—that integrate local sequence features (k-mers) and contextual embeddings via convolutional neural networks to improve predictive performance and generalization. We evaluate these models using both a Random-Split strategy and a more biologically realistic Leave-One-Chromosome-Out setting to ensure robustness across genomic regions. Our proposed models outperform the state-of-the-art m6A-TCPred model across all key evaluation metrics. Hybrid Deep Model achieves the highest accuracy under Random-Split, while Hybrid Model demonstrates superior generalization under Leave-One-Chromosome-Out, indicating that deep global representations may overfit in chromosome-independent settings. These findings underscore the importance of rigorous validation strategies and offer insights into designing robust m6A predictors. Availability and implementation Source code and datasets are available at: https://github.com/malikmtahir/LOCO-m6A
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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