Papers › HyenaDNA: Long-Range Genomic Sequence Modeling at Single Nucleotide Resolution

HyenaDNA: Long-Range Genomic Sequence Modeling at Single Nucleotide Resolution

27 Jun 2023NeurIPS 2023 11arXiv:2306.15794archive 2025-07-28

Eric Nguyen, Michael Poli, Marjan Faizi, Armin Thomas, Callum Birch-Sykes, Michael Wornow, Aman Patel, Clayton Rabideau, Stefano Massaroli, Yoshua Bengio, Stefano Ermon, Stephen A. Baccus, Chris Ré

Genomic (DNA) sequences encode an enormous amount of information for gene regulation and protein synthesis. Similar to natural language models, researchers have proposed foundation models in genomics to learn generalizable features from unlabeled genome data that can then be fine-tuned for downstream tasks such as identifying regulatory elements. Due to the quadratic scaling of attention, previous Transformer-based genomic models have used 512 to 4k tokens as context (<0.001% of the human genome), significantly limiting the modeling of long-range interactions in DNA. In addition, these methods rely on tokenizers or fixed k-mers to aggregate meaningful DNA units, losing single nucleotide resolution where subtle genetic variations can completely alter protein function via single nucleotide polymorphisms (SNPs). Recently, Hyena, a large language model based on implicit convolutions was shown to match attention in quality while allowing longer context lengths and lower time complexity. Leveraging Hyena's new long-range capabilities, we present HyenaDNA, a genomic foundation model pretrained on the human reference genome with context lengths of up to 1 million tokens at the single nucleotide-level - an up to 500x increase over previous dense attention-based models. HyenaDNA scales sub-quadratically in sequence length (training up to 160x faster than Transformer), uses single nucleotide tokens, and has full global context at each layer. We explore what longer context enables - including the first use of in-context learning in genomics. On fine-tuned benchmarks from the Nucleotide Transformer, HyenaDNA reaches state-of-the-art (SotA) on 12 of 18 datasets using a model with orders of magnitude less parameters and pretraining data. On the GenomicBenchmarks, HyenaDNA surpasses SotA on 7 of 8 datasets on average by +10 accuracy points. Code at https://github.com/HazyResearch/hyena-dna.

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HazyResearch/hyena-dna officialmentioned in papermentioned on GitHubpytorch report
frederikkemarin/bend mentioned on GitHubpytorchBSD-3-Clause report
jimmylihui/OpenGenome mentioned on GitHubpytorch report
jimmylihui/genbench mentioned on GitHubpytorchApache-2.0 report

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Activation HazyResearch/hyena-dna/src/models/sequence/hyena.py official repository ran · our draft was wrong Apache-2.0 (permissive) · 3cd2f572b4362749 · report
Laplace HazyResearch/hyena-dna/src/models/sequence/hyena.py official repository ran fingerprinted Apache-2.0 (permissive) · 916ff67d7cc5dec1 · report
SquaredReLU HazyResearch/hyena-dna/src/models/sequence/hyena.py official repository ran fingerprinted Apache-2.0 (permissive) · 2c0fd690964e38f6 · report
TransposedLN HazyResearch/hyena-dna/src/models/sequence/hyena.py official repository ran · metamorphic tier: deterministic fingerprinted Apache-2.0 (permissive) · f930c490ea93d623 · report
laplace HazyResearch/hyena-dna/src/models/sequence/hyena.py official repository ran · our draft was wrong fingerprinted Apache-2.0 (permissive) · 452d521c52ebdf0f · report
HyenaOperator HazyResearch/hyena-dna/src/models/sequence/hyena.py official repository unverified Apache-2.0 (permissive) · bdfcfc1b78dd3774 · report
auto_assign_attrs HazyResearch/hyena-dna/src/models/sequence/hyena.py official repository unverified Apache-2.0 (permissive) · b37e90eb829295dc · report
instantiate HazyResearch/hyena-dna/src/models/sequence/hyena.py official repository unverified Apache-2.0 (permissive) · ef3e1ed020307a6f · report
ExponentialModulation frederikkemarin/bend/bend/models/hyena_dna.py community (archive-listed) ran BSD-3-Clause (permissive) · 71c56d498ff19d96 · report
GPT2Embeddings frederikkemarin/bend/bend/models/hyena_dna.py community (archive-listed) ran BSD-3-Clause (permissive) · fb99304499c57d08 · report
HyenaFilter frederikkemarin/bend/bend/models/hyena_dna.py community (archive-listed) ran BSD-3-Clause (permissive) · b65ebc2556b1f0bd · report
LinearResidual frederikkemarin/bend/bend/models/hyena_dna.py community (archive-listed) ran BSD-3-Clause (permissive) · e9b64f401a36c5e0 · report
MHA frederikkemarin/bend/bend/models/hyena_dna.py community (archive-listed) ran BSD-3-Clause (permissive) · 2108a9e482ae37a6 · report
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Block frederikkemarin/bend/bend/models/hyena_dna.py community (archive-listed) unverified BSD-3-Clause (permissive) · 15e87d04566e903e · report
HyenaDNAModel frederikkemarin/bend/bend/models/hyena_dna.py community (archive-listed) unverified BSD-3-Clause (permissive) · 1a0693ded9212e71 · report
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LMBackbone frederikkemarin/bend/bend/models/hyena_dna.py community (archive-listed) unverified BSD-3-Clause (permissive) · 989ba1bad54bbbc8 · report
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fftconv frederikkemarin/bend/bend/models/hyena_dna.py community (archive-listed) unverified BSD-3-Clause (permissive) · 41b32f57fc8ec1e5 · report
mul_sum identical code first harvested elsewhere ran · fixture could not drive it licence of this copy not recorded · 5dd28d20c60f0c19 · report

Tasks

4kIn-Context LearningLanguage ModellingLarge Language Model

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Methods

Absolute Position EncodingsAdamAttentionBPEDense ConnectionsDropoutLabel SmoothingLayer NormalizationLinear LayerMulti-Head AttentionPosition-Wise Feed-Forward LayerResidual ConnectionSoftmaxTransformer

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