The authors develop mRNABERT, a foundational AI model that designs entire mRNA sequences and demonstrates superior performance across comprehensive benchmarks, which signifies a substantial leap forward in mRNA research and therapeutic development.
Abstract
Designing effective mRNA sequences for therapeutics remains a formidable challenge. Inspired by successes in protein design, language models (LMs) are now being applied to RNA, but progress is often impeded by the lack of comprehensive training data. Existing models are frequently limited to UTR or CDS regions, restricting their application for complete mRNA sequences. We introduce mRNABERT, a robust, all-in-one mRNA designer pre-trained on the largest available mRNA dataset. To enhance performance, we propose a dual tokenization scheme with a cross-modality contrastive learning framework to integrate semantic information from protein sequences. On a comprehensive benchmark, mRNABERT demonstrates state-of-the-art performance, outperforming previous models in the majority of tasks for 5’ UTR and CDS design, RNA-binding protein (RBP) site prediction, and full-length mRNA property prediction. It also surpasses large protein models in several related tasks. In conclusion, mRNABERT’s superior performance across these diverse tasks signifies a substantial leap forward in mRNA research and therapeutic development. Designing complete mRNA sequences for new vaccines and therapies is a complex challenge. Here, the authors develop mRNABERT, a foundational AI model that designs entire mRNA sequences and demonstrates superior performance across comprehensive benchmarks.
Parnet is a multi-task foundation model trained end-to-end on 223 eCLIP-seq experiments spanning 150 RBPs to predict base-resolution RBP binding profiles directly from RNA sequence, and establishes the RBP interactome as a compact, functionally sufficient, and interpretable basis for foundation model pretraining in RNA biology.
In recent years, deep-learning has revolutionized protein structure prediction, achieving remarkable speed and accuracy. RNA structure prediction, however, has lagged behind. Although several methods have shown moderate success in predicting RNA secondary and tertiary structures, none have reached the accuracy observed with contemporary protein models. The lack of success of these RNA structure prediction models has been proposed to be due to limited high-quality structural information that can be used as training data. To probe this proposed limitation, we developed a large and diverse dataset comprising paired RNA sequences and their corresponding secondary structures. We assessed the utility of this enhanced dataset by retraining on a deep-learning model, SincFold. We find that SincFold exhibited improved performance on a set of previously unseen RNA families, enhancing its capability to predict accurate de novo RNA secondary structures. We additionally implemented Lyra-TransPred, which achieved the highest mean F1 and MCC among the evaluated models while requiring substantially less training time per epoch. The RNASSTR dataset provides a substantial advance for RNA structure modeling, laying a strong foundation for the development of future RNA secondary structure prediction algorithms.
Conner J. Langeberg, Taehan Kim, Roma Nagle et al.· RNA: A publication of the RN...· 0 citations
Long non-coding RNAs (lncRNAs) play important roles in gene regulation, development and disease, yet accurate identification of lncRNAs from transcriptomic data remains a major computational challenge. Existing methods often rely either on handcrafted sequence features or deep learning approaches, each with inherent limitations in capturing the full complexity of RNA sequences. In this study, we proposed HyLnc, a computational framework that integrates transformer-based contextual embeddings with biologically meaningful sequence features for improved lncRNA prediction. A custom BERT-based model was first pre-trained on a large corpus of metazoan RNA sequences using a masked language modelling strategy to learn contextual nucleotide dependencies. The model was subsequently fine-tuned on curated datasets of lncRNAs and protein-coding transcripts and 256-dimensional deep sequence embeddings were extracted. Parallelly, 348 handcrafted features, including ORF characteristics, untranslated region (UTR) properties, nucleotide composition and Fickett scores, were computed. A multi-stage feature selection strategy was applied to identify the most informative features, resulting in optimized hybrid feature sets. Multiple machine learning classifiers were evaluated, with the RF model achieving the best performance. The proposed framework attained an accuracy of 91.30%, F1-score of 91.23% and MCC 82.60 on an independent validation dataset, outperforming several existing lncRNA prediction tools. Thus, HyLnc demonstrates that integrating deep contextual representations with biologically interpretable features enhances lncRNA prediction. This approach provides a robust and scalable solution for large-scale transcriptome annotation and can be extended to other sequence-based prediction.
GB.GeneUnet, an 837M-parameter transformer-based U-Net pretrained on 6 trillion tokens from multi-species genomes in OpenGenome2 is introduced, extending genomic context to 1 Mb with up to 100× inference speedup over GeneMoE, a preliminary MoE transformer baseline of similar model size pretrained on the same data.
Ning Sun, William de Vazelhes, Pan Li et al.· bioRxiv· 0 citations
RNA motifs and Low-Complexity Repeats (LCRs)—recurrent, conserved sequences of nucleotides—serve as the fundamental vocabulary of RNA structure and biological function. While current RNA foundation models have revolutionized sequence modeling through Transformer architectures, they predominantly prioritize modeling global dependencies within the raw sequence. To address this limitation, we propose MotRNA, a motif-aware RNA language model integrating an Explicit N-gram Memory mechanism. Unlike standard implicit neural modeling, MotRNA employs a conditional memory module to explicitly retrieve and fuse motif embeddings based on input k-mers. This mechanism provides direct access to strictly defined local patterns, complementing the global context modeled by self-attention. We validate MotRNA on large-scale RNA datasets. The model achieves a 9.6% absolute improvement in Masked Language Modeling (MLM) accuracy at a 30% masking ratio compared to state-of-the-art baselines. Notably, MotRNA maintains high robustness under extreme masking ratios, indicating effective biological signal reconstruction from sparse context. Crucially, our analysis reveals that the backbone encoder becomes self-contained post-training: the memory module facilitates the internalization of motif semantics into the model parameters, allowing the backbone to retain performance advantages even when the memory is detached during inference.
Xiang-Yu Ji, Xin Wang, Yang Zhang et al.· Proceedings of the 32nd ACM...· 0 citations
It is shown that single-sequence PLMs can perform in-context peptide learning without gradient updates, task-specific retraining, or architectural modification, and MPEP conditioning is established as a lightweight strategy for low-data peptide classification.
Joshua Almonte, Minh N. Vu, Andrew Ahn et al.· bioRxiv· 0 citations
What does it take to trust AI-driven HVAC optimization? Our AI Model Factory combines agents, machine learning, reinforcement learning and deterministic checks in a governed workflow designed for messy, real-world building data. The post We built an AI factory for HVAC control appeared first on GPT-Lab.
MIT News · Artificial Intelligence· news.mit.eduAug 18, 2026
A new method for surgically removing training examples from a model reveals that as datasets grow, the link between what a model learns and what it produces dissolves.
MIT News · Artificial Intelligence· news.mit.eduMay 20, 2026
