An RNA foundation model enables discovery of disease mechanisms and candidate therapeutics
Bibliographic record
Abstract
Abstract Accurately modeling and predicting RNA biology has been a long-standing challenge, bearing significant clinical ramifications for variant interpretation and the formulation of tailored therapeutics. We describe a foundation model for RNA biology, “BigRNA”, which was trained on thousands of genome-matched datasets to predict tissue-specific RNA expression, splicing, microRNA sites, and RNA binding protein specificity from DNA sequence. Unlike approaches that are restricted to missense variants, BigRNA can identify pathogenic non-coding variant effects across diverse mechanisms, including polyadenylation, exon skipping and intron retention. BigRNA accurately predicted the effects of steric blocking oligonucleotides (SBOs) on increasing the expression of 4 out of 4 genes, and on splicing for 18 out of 18 exons across 14 genes, including those involved in Wilson disease and spinal muscular atrophy. We anticipate that BigRNA and foundation models like it will have widespread applications in the field of personalized RNA therapeutics.
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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".