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

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.

How to Build the Virtual Cell with Artificial Intelligence: Priorities and Opportunities

The cell is arguably the smallest unit of life and is central to understanding biology. Accurate modeling of cells is important for this understanding as well as for determining the root causes of disease. Recent advances in artificial intelligence (AI), combined with the ability to generate large-scale experimental data, present novel opportunities to model cells. Here we propose a vision of AI-powered Virtual Cells, where robust representations of cells and cellular systems under different conditions are directly learned from growing biological data across measurements and scales. We discuss desired capabilities of AI Virtual Cells, including generating universal representations of biological entities across scales, and facilitating interpretable in silico experiments to predict and understand their behavior using Virtual Instruments. We further address the challenges, opportunities and requirements to realize this vision including data needs, evaluation strategies, and community standards and engagement to ensure biological accuracy and broad utility. We envision a future where AI Virtual Cells help identify new drug targets, predict cellular responses to perturbations, as well as scale hypothesis exploration. With open science collaborations across the biomedical ecosystem that includes academia, philanthropy, and the biopharma and AI industries, a comprehensive predictive understanding of cell mechanisms and interactions is within reach.