JEPA-DNA: Grounding Genomic Foundation Models through Joint-Embedding Predictive Architectures
About
Genomic Foundation Models (GFMs) typically rely on Masked Language Modeling (MLM) or Next-Token Prediction (NTP) to learn the "Laws of Nature". While effective at capturing local syntax, these generative paradigms prioritize token-level reconstruction over high-level functional context. We introduce JEPA-DNA, a model-agnostic continual training framework that integrates a Joint-Embedding Predictive Architecture (JEPA) with traditional generative objectives. By supervising global sequence embeddings in a latent space, JEPA-DNA forces models to predict the functional representations of masked genomic segments, shifting the learning signal from token recovery to semantic alignment. We evaluate JEPA-DNA on 17 diverse genomic benchmark tasks, demonstrating consistent gains in linear probing and zero-shot performance regardless of the underlying GFM architecture or generative objective. Our framework establishes a new state-of-the-art for GFMs, surpassing the best existing models by bridging generative precision with latent semantic grounding. Through extensive ablation studies, we further characterize the synergistic interplay between generative and latent objectives. Our code is publicly available at https://github.com/NVIDIA-Digital-Bio/JEPA-DNA.
Related benchmarks
| Task | Dataset | Result | Rank | |
|---|---|---|---|---|
| Disease Variant Prediction | BEND Disease Variant | AUROC0.512 | 2 | |
| Expression Effect Prediction | BEND Expression Effect | AUROC0.524 | 2 | |
| Variant Effect Prediction | TraitGym Mendelian | AUROC0.544 | 2 | |
| Variant Effect Prediction | Songlab ClinVar | AUROC0.544 | 2 | |
| Pathogenicity Prediction | LRB Pathogenic OMIM | AUROC0.452 | 2 | |
| Variant Effect Prediction | TraitGym Complex | AUROC49.1 | 2 |