Methodological challenges in constructing DNA methylation risk scores
Bibliographic record
Abstract
Polygenic approaches often access more variance of complex traits than is possible by single variant approaches. For genotype data, genetic risk scores (GRS) are widely used for risk prediction as well as in association and interaction studies. Recently, interest has been growing in transferring GRS approaches to DNA methylation data (methylation risk scores, MRS), which can be used 1) as biomarkers for environmental exposures, 2) in association analyses in which single CpG sites do not achieve significance, 3) as dimension reduction approach in interaction and mediation analyses, and 4) to predict individual risks of disease or treatment success. Most GRS approaches can directly be transferred to methylation data. However, since methylation data is more sensitive to confounding, e.g. by age and tissue, it is more complex to find appropriate external weights. In this review, we will outline the adaption of current GRS approaches to methylation data and highlight occurring challenges.
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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 | 0.019 | 0.033 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".