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Multi-purpose RNA language modelling with motif-aware pretraining and type-guided fine-tuning

Ning Wang, 将尚 渡辺, Yuchen Li, Xuhong Li, Shahid Mumtaz, Linghe Kong, Haoyi Xiong

2024Nature Machine Intelligence119 citationsDOIOpen Access PDF

Abstract

Abstract Pretrained language models have shown promise in analysing nucleotide sequences, yet a versatile model excelling across diverse tasks with a single pretrained weight set remains elusive. Here we introduce RNAErnie, an RNA-focused pretrained model built upon the transformer architecture, employing two simple yet effective strategies. First, RNAErnie enhances pretraining by incorporating RNA motifs as biological priors and introducing motif-level random masking in addition to masked language modelling at base/subsequence levels. It also tokenizes RNA types (for example, miRNA, lnRNA) as stop words, appending them to sequences during pretraining. Second, subject to out-of-distribution tasks with RNA sequences not seen during the pretraining phase, RNAErnie proposes a type-guided fine-tuning strategy that first predicts possible RNA types using an RNA sequence and then appends the predicted type to the tail of sequence to refine feature embedding in a post hoc way. Our extensive evaluation across seven datasets and five tasks demonstrates the superiority of RNAErnie in both supervised and unsupervised learning. It surpasses baselines with up to 1.8% higher accuracy in classification, 2.2% greater accuracy in interaction prediction and 3.3% improved F1 score in structure prediction, showcasing its robustness and adaptability with a unified pretrained foundation.

Topics & Concepts

Motif (music)Computer scienceRNABiologyPhysicsGeneGeneticsAcousticsRNA and protein synthesis mechanismsRNA Research and SplicingRNA modifications and cancer
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