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Main Authors: Schiff, Yair, Kao, Chia-Hsiang, Gokaslan, Aaron, Dao, Tri, Gu, Albert, Kuleshov, Volodymyr
Format: Preprint
Published: 2024
Subjects:
Online Access:https://arxiv.org/abs/2403.03234
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author Schiff, Yair
Kao, Chia-Hsiang
Gokaslan, Aaron
Dao, Tri
Gu, Albert
Kuleshov, Volodymyr
author_facet Schiff, Yair
Kao, Chia-Hsiang
Gokaslan, Aaron
Dao, Tri
Gu, Albert
Kuleshov, Volodymyr
contents Large-scale sequence modeling has sparked rapid advances that now extend into biology and genomics. However, modeling genomic sequences introduces challenges such as the need to model long-range token interactions, the effects of upstream and downstream regions of the genome, and the reverse complementarity (RC) of DNA. Here, we propose an architecture motivated by these challenges that builds off the long-range Mamba block, and extends it to a BiMamba component that supports bi-directionality, and to a MambaDNA block that additionally supports RC equivariance. We use MambaDNA as the basis of Caduceus, the first family of RC equivariant bi-directional long-range DNA language models, and we introduce pre-training and fine-tuning strategies that yield Caduceus DNA foundation models. Caduceus outperforms previous long-range models on downstream benchmarks; on a challenging long-range variant effect prediction task, Caduceus exceeds the performance of 10x larger models that do not leverage bi-directionality or equivariance.
format Preprint
id arxiv_https___arxiv_org_abs_2403_03234
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Caduceus: Bi-Directional Equivariant Long-Range DNA Sequence Modeling
Schiff, Yair
Kao, Chia-Hsiang
Gokaslan, Aaron
Dao, Tri
Gu, Albert
Kuleshov, Volodymyr
Genomics
Machine Learning
Large-scale sequence modeling has sparked rapid advances that now extend into biology and genomics. However, modeling genomic sequences introduces challenges such as the need to model long-range token interactions, the effects of upstream and downstream regions of the genome, and the reverse complementarity (RC) of DNA. Here, we propose an architecture motivated by these challenges that builds off the long-range Mamba block, and extends it to a BiMamba component that supports bi-directionality, and to a MambaDNA block that additionally supports RC equivariance. We use MambaDNA as the basis of Caduceus, the first family of RC equivariant bi-directional long-range DNA language models, and we introduce pre-training and fine-tuning strategies that yield Caduceus DNA foundation models. Caduceus outperforms previous long-range models on downstream benchmarks; on a challenging long-range variant effect prediction task, Caduceus exceeds the performance of 10x larger models that do not leverage bi-directionality or equivariance.
title Caduceus: Bi-Directional Equivariant Long-Range DNA Sequence Modeling
topic Genomics
Machine Learning
url https://arxiv.org/abs/2403.03234