<scp>ADAR-GPT</scp> : A continually fine-tuned language model for predicting A-to-I RNA editing sites

Adenosine-to-inosine (A-to-I) RNA editing by ADAR enzymes shapes transcript fate and underpins emerging RNA editing therapeutics, yet predicting which adenosines are edited remains difficult. We introduce ADAR-GPT, a model-agnostic fine-tuning framework that adapts a GPT-class language model to classify editing at candidate sites using sequence context in standardized 201 nt windows with the target adenosine explicitly marked. We train and evaluate on GTEx liver data ([Formula: see text] samples) at a clinically relevant 15% editing threshold, using a two-stage continual fine-tuning approach where lower thresholds serve as curriculum data to progressively sharpen decision boundaries. Using sequence data, ADAR-GPT demonstrates competitive or superior performance when benchmarked against established computational approaches, including convolutional and foundation model architectures, achieving a better balance of recall, precision, and specificity alongside stronger operating-curve metrics. The approach is reproducible and portable across GPT backbones without architectural changes. Beyond accurate site classification, ADAR-GPT provides practical adenosine scoring to prioritize experimental targets and inform guide RNA design, with a framework adaptable to new datasets and model architectures.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2026-01-09
DOI
https://doi.org/10.1073/pnas.2529073123
Citations
2
Primary Topic
RNA regulation and disease
Type
article
Field-Weighted Citation Impact
44.47

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article

ADAR-GPT : A continually fine-tuned language model for predicting A-to-I RNA editing sites

Gal Oren, Erez Y. Levanon, Zohar Rosenwasser, Roni Cohen-Fultheim et al.
2 citations
Proceedings of the National Academy of Sciences
RNA regulation and disease
44.47
article

ADAR-GPT : A continually fine-tuned language model for predicting A-to-I RNA editing sites

Gal Oren, Erez Y. Levanon, Zohar Rosenwasser, Roni Cohen-Fultheim, Michael Levitt
article en
2 citations

Abstract

Adenosine-to-inosine (A-to-I) RNA editing by ADAR enzymes shapes transcript fate and underpins emerging RNA editing therapeutics, yet predicting which adenosines are edited remains difficult. We introduce ADAR-GPT, a model-agnostic fine-tuning framework that adapts a GPT-class language model to classify editing at candidate sites using sequence context in standardized 201 nt windows with the target adenosine explicitly marked. We train and evaluate on GTEx liver data ([Formula: see text] samples) at a clinically relevant 15% editing threshold, using a two-stage continual fine-tuning approach where lower thresholds serve as curriculum data to progressively sharpen decision boundaries. Using sequence data, ADAR-GPT demonstrates competitive or superior performance when benchmarked against established computational approaches, including convolutional and foundation model architectures, achieving a better balance of recall, precision, and specificity alongside stronger operating-curve metrics. The approach is reproducible and portable across GPT backbones without architectural changes. Beyond accurate site classification, ADAR-GPT provides practical adenosine scoring to prioritize experimental targets and inform guide RNA design, with a framework adaptable to new datasets and model architectures.

Proceedings of the National Academy of SciencesVol. 123(2)
Technion – Israel Institute of Technology (IL), Goodman Research Group (United States) (US), Indiana University School of Medicine, Stanford University (US)
National Institutes of Health
Quality Education
Openalex Percentile: Top 0%
RNA regulation and disease
44.47
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<scp>ADAR-GPT</scp> : A continually fine-tuned language model for predicting A-to-I RNA editing sites — Gal Oren, Erez Y. Levanon, et al. · Proceedings of the National Academy of Sciences (2026) | TGRS Research Map | TGRS