English

dnaHNet: A Scalable and Hierarchical Foundation Model for Genomic Sequence Learning

Machine Learning 2026-04-13 v3

Abstract

Genomic foundation models have the potential to decode DNA syntax, yet face a fundamental tradeoff in their input representation. Standard fixed-vocabulary tokenizers fragment biologically meaningful motifs such as codons and regulatory elements, while nucleotide-level models preserve biological coherence but incur prohibitive computational costs for long contexts. We introduce dnaHNet, a state-of-the-art tokenizer-free autoregressive model that segments and models genomic sequences end-to-end. Using a differentiable dynamic chunking mechanism, dnaHNet compresses raw nucleotides into latent tokens adaptively, balancing compression with predictive accuracy. Pretrained on prokaryotic genomes, dnaHNet outperforms leading architectures including StripedHyena2 in scaling and efficiency. This recursive chunking yields quadratic FLOP reductions, enabling >3×>3 \times inference speedup over Transformers. On zero-shot tasks, dnaHNet achieves superior performance in predicting protein variant fitness and gene essentiality, while automatically discovering hierarchical biological structures without supervision. These results establish dnaHNet as a scalable, interpretable framework for next-generation genomic modeling.

Keywords

Cite

@article{arxiv.2602.10603,
  title  = {dnaHNet: A Scalable and Hierarchical Foundation Model for Genomic Sequence Learning},
  author = {Arnav Shah and Junzhe Li and Parsa Idehpour and Adibvafa Fallahpour and Brandon Wang and Sukjun Hwang and Bo Wang and Patrick D. Hsu and Hani Goodarzi and Albert Gu},
  journal= {arXiv preprint arXiv:2602.10603},
  year   = {2026}
}
R2 v1 2026-07-01T10:31:27.119Z