Cross-species modeling of plant genomes at single nucleotide resolution using a pre-trained DNA language model
Zhai, J.; Gokaslan, A.; Schiff, Y.; Berthel, A.; Liu, Z.-Y.; Lai, W.-Y.; Miller, Z. R.; Scheben, A.; Stitzer, M. C.; Romay, C.; Buckler, E. S.; Kuleshov, V.
Show abstract
Interpreting function and fitness effects in diverse plant genomes requires transferable models. Language models (LMs) pre-trained on large-scale biological sequences can learn evolutionary conservation and offer cross-species prediction better than supervised models through fine-tuning limited labeled data. We introduce PlantCaduceus, a plant DNA LM based on the Caduceus and Mamba architectures, pre-trained on a curated dataset of 16 Angiosperm genomes. Fine-tuning PlantCaduceus on limited labeled Arabidopsis data for four tasks, including predicting translation initiation/termination sites and splice donor and acceptor sites, demonstrated high transferability to 160 million year diverged maize, outperforming the best existing DNA LM by 1.45 to 7.23-fold. PlantCaduceus is competitive to state-of-the-art protein LMs in terms of deleterious mutation identification, and is threefold better than PhyloP. Additionally, PlantCaduceus successfully identifies well-known causal variants in both Arabidopsis and maize. Overall, PlantCaduceus is a versatile DNA LM that can accelerate plant genomics and crop breeding applications.
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