Caduceus: Bi-Directional Equivariant Long-Range DNA Sequence Modeling
About
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.
Related benchmarks
| Task | Dataset | Result | Rank | |
|---|---|---|---|---|
| Gene Expression CAGE Prediction | K562 | MSE0.1959 | 10 | |
| Gene Expression CAGE Prediction | GM12878 | MSE0.1942 | 10 | |
| Classification | Genomic Benchmarks | Mouse Enhancers Accuracy81 | 5 | |
| Histone mark prediction | Nucleotide Transformer benchmark | H3 Accuracy80.48 | 5 | |
| Regulatory element prediction | Nucleotide Transformer benchmark | Enhancer Accuracy55.2 | 5 | |
| Variant Effect Prediction | Human SNP 0–30k distance-to-TSS bin | AUROC0.678 | 5 | |
| Variant Effect Prediction | Human SNP (100k+ distance-to-TSS bin) | AUROC58 | 5 | |
| Variant Effect Prediction | Human SNP 30–100k distance-to-TSS bin | AUROC0.648 | 5 | |
| Splice site identification | Nucleotide Transformer benchmark | Splice Acceptor Accuracy94.21 | 5 | |
| Sequence Classification | Genomic Benchmarks Human vs. Worm (test) | Top-1 Accuracy97.3 | 4 |