# HybriDNA: A Hybrid Transformer-Mamba2 Long-Range DNA Language Model

arXiv: https://arxiv.org/abs/2502.10807 · HTML: https://mlsanity.com/paper/2502.10807/

## Key facts

- Cited by 7 papers in the map (data through 14 Oct 2026).
- Builds on 28 of its 51 references that are in the map.
- First posted on arXiv 15 Feb 2025.

## Builds on (most cited first, 28 of 28)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [GPT-4 Technical Report](https://mlsanity.com/paper/2303.08774/) (2023)
- [RoFormer: Enhanced Transformer with Rotary Position Embedding](https://mlsanity.com/paper/2104.09864/) (2021)
- [Neural Machine Translation by Jointly Learning to Align and Translate](https://mlsanity.com/paper/1409.0473/) (2014)
- [On the Opportunities and Risks of Foundation Models](https://mlsanity.com/paper/2108.07258/) (2021)
- [FlashAttention-2: Faster Attention with Better Parallelism and Work Partitioning](https://mlsanity.com/paper/2307.08691/) (2023)
- [Efficiently Modeling Long Sequences with Structured State Spaces](https://mlsanity.com/paper/2111.00396/) (2021)
- [Root Mean Square Layer Normalization](https://mlsanity.com/paper/1910.07467/) (2019)
- [Transformers are SSMs: Generalized Models and Efficient Algorithms Through Structured State Space Duality](https://mlsanity.com/paper/2405.21060/) (2024)
- [Simplified State Space Layers for Sequence Modeling](https://mlsanity.com/paper/2208.04933/) (2022)
- [Combining Recurrent, Convolutional, and Continuous-time Models with Linear State-Space Layers](https://mlsanity.com/paper/2110.13985/) (2021)
- [Hungry Hungry Hippos: Towards Language Modeling with State Space Models](https://mlsanity.com/paper/2212.14052/) (2022)
- [On the Parameterization and Initialization of Diagonal State Space Models](https://mlsanity.com/paper/2206.11893/) (2022)
- [Jamba: A Hybrid Transformer-Mamba Language Model](https://mlsanity.com/paper/2403.19887/) (2024)
- [Hyena Hierarchy: Towards Larger Convolutional Language Models](https://mlsanity.com/paper/2302.10866/) (2023)
- [Diagonal State Spaces are as Effective as Structured State Spaces](https://mlsanity.com/paper/2203.14343/) (2022)
- [An Empirical Study of Mamba-based Language Models](https://mlsanity.com/paper/2406.07887/) (2024)
- [Samba: Simple Hybrid State Space Models for Efficient Unlimited Context Language Modeling](https://mlsanity.com/paper/2406.07522/) (2024)
- [DNABERT-2: Efficient Foundation Model and Benchmark For Multi-Species Genome](https://mlsanity.com/paper/2306.15006/) (2023)
- [Zamba: A Compact 7B SSM Hybrid Model](https://mlsanity.com/paper/2405.16712/) (2024)
- [Caduceus: Bi-Directional Equivariant Long-Range DNA Sequence Modeling](https://mlsanity.com/paper/2403.03234/) (2024)
- [Repetition Improves Language Model Embeddings](https://mlsanity.com/paper/2402.15449/) (2024)
- [BEND: Benchmarking DNA Language Models on biologically meaningful tasks](https://mlsanity.com/paper/2311.12570/) (2023)
- [GENERator: A Long-Context Generative Genomic Foundation Model](https://mlsanity.com/paper/2502.07272/) (2025)
- [Taipan: Efficient and Expressive State Space Language Models with Selective Attention](https://mlsanity.com/paper/2410.18572/) (2024)
- [SFM-Protein: Integrative Co-evolutionary Pre-training for Advanced Protein Sequence Representation](https://mlsanity.com/paper/2410.24022/) (2024)

## Built on by (most cited first, 7 of 7)

- [JanusDNA: A Powerful Bi-directional Hybrid DNA Foundation Model](https://mlsanity.com/paper/2505.17257/) (2025)
- [MergeDNA: Context-aware Genome Modeling with Dynamic Tokenization through Token Merging](https://mlsanity.com/paper/2511.14806/) (2025)
- [Reverse-Complement Consistency for DNA Language Models](https://mlsanity.com/paper/2509.18529/) (2025)
- [Event Fields: Learning Latent Event Structure for Waveform Foundation Models](https://mlsanity.com/paper/2605.08685/) (2026)
- [WISTERIA: Learning Clinical Representations from Noisy Supervision via Multi-View Consistency in Electronic Health Records](https://mlsanity.com/paper/2605.09765/) (2026)
- [AURORA: Contextual Orthogonalization for Geometric Representation Learning in Healthcare Foundation Models](https://mlsanity.com/paper/2605.17765/) (2026)
- [GENEB: Why Genomic Models Are Hard to Compare](https://mlsanity.com/paper/2606.04525/) (2026)

## Abstract (arXiv)

Advances in natural language processing and large language models have sparked growing interest in modeling DNA, often referred to as the "language of life". However, DNA modeling poses unique challenges. First, it requires the ability to process ultra-long DNA sequences while preserving single-nucleotide resolution, as individual nucleotides play a critical role in DNA function. Second, success in this domain requires excelling at both generative and understanding tasks: generative tasks hold potential for therapeutic and industrial applications, while understanding tasks provide crucial insights into biological mechanisms and diseases. To address these challenges, we propose HybriDNA, a decoder-only DNA language model that incorporates a hybrid Transformer-Mamba2 architecture, seamlessly integrating the strengths of attention mechanisms with selective state-space models. This hybrid design enables HybriDNA to efficiently process DNA sequences up to 131kb in length with single-nucleotide resolution. HybriDNA achieves state-of-the-art performance across 33 DNA understanding datasets curated from the BEND, GUE, and LRB benchmarks, and demonstrates exceptional capability in generating synthetic cis-regulatory elements (CREs) with desired properties. Furthermore, we show that HybriDNA adheres to expected scaling laws, with performance improving consistently as the model scales from 300M to 3B and 7B parameters. These findings underscore HybriDNA's versatility and its potential to advance DNA research and applications, paving the way for innovations in understanding and engineering the "language of life".