[2602.10603] dnaHNet: A Scalable and Hierarchical Foundation Model for Genomic Sequence Learning
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 $>3 \times$ 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.
View PDF HTML (experimental) 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…
saved by
related reading
- You Can Learn Tokenization End-to-End with Reinforcement Learningarxiv.org
- H-Nets - the Past | Goomba Labgoombalab.github.io
- Dynamic Chunking for End-to-End Hierarchical Sequence Modelingarxiv.org
- Aman's AI Journal • Primers • Ilya Sutskever's Top 30aman.ai
- Evo 2: DNA Foundation Model | Arc Institutearcinstitute.org
- A socratic dialogue over the utility of DNA language models (Part 1 of 2)owlposting.com
- Advancing regulatory variant effect prediction with AlphaGenomenature.com
- AlphaGenome: AI for better understanding the genome — Google DeepMinddeepmind.google
- Evo 2 Can Design Entire Genomesasimov.press
- Evo 2: DNA Foundation Model | Arc Institutearcinstitute.org
- Genome modelling and design across all domains of life with Evo 2 | Naturenature.com
- Publications - Debbie Marks Labdeboramarkslab.com