Jiayang Chen

Tao Shen, Zhihang Hu, Siqi Sun et al.

Accurate prediction of RNA three-dimensional (3D) structure remains an unsolved challenge. Determining RNA 3D structures is crucial for understanding their functions and informing RNA-targeting drug development and synthetic biology design. The structural flexibility of RNA, which leads to scarcity of experimentally determined data, complicates computational prediction efforts. Here, we present RhoFold+, an RNA language model-based deep learning method that accurately predicts 3D structures of single-chain RNAs from sequences. By integrating an RNA language model pre-trained on ~23.7 million RNA sequences and leveraging techniques to address data scarcity, RhoFold+ offers a fully automated end-to-end pipeline for RNA 3D structure prediction. Retrospective evaluations on RNA-Puzzles and CASP15 natural RNA targets demonstrate RhoFold+'s superiority over existing methods, including human expert groups. Its efficacy and generalizability are further validated through cross-family and cross-type assessments, as well as time-censored benchmarks. Additionally, RhoFold+ predicts RNA secondary structures and inter-helical angles, providing empirically verifiable features that broaden its applicability to RNA structure and function studies.

Le Zhang, Jiayang Chen, Tao Shen et al. · mila

The field of protein folding research has been greatly advanced by deep learning methods, with AlphaFold2 (AF2) demonstrating exceptional performance and atomic-level precision. As co-evolution is integral to protein structure prediction, AF2's accuracy is significantly influenced by the depth of multiple sequence alignment (MSA), which requires extensive exploration of a large protein database for similar sequences. However, not all protein sequences possess abundant homologous families, and consequently, AF2's performance can degrade on such queries, at times failing to produce meaningful results. To address this, we introduce a novel generative language model, MSA-Augmenter, which leverages protein-specific attention mechanisms and large-scale MSAs to generate useful, novel protein sequences not currently found in databases. These sequences supplement shallow MSAs, enhancing the accuracy of structural property predictions. Our experiments on CASP14 demonstrate that MSA-Augmenter can generate de novo sequences that retain co-evolutionary information from inferior MSAs, thereby improving protein structure prediction quality on top of strong AF2.

Zefeng Lin, Yi Xiao, Zhiqiang Mo et al.

Automatically adapting novels into screenplays is important for the TV, film, or opera industries to promote products with low costs. The strong performances of large language models (LLMs) in long-text generation call us to propose a LLM based framework Reader-Rewriter (R$^2$) for this task. However, there are two fundamental challenges here. First, the LLM hallucinations may cause inconsistent plot extraction and screenplay generation. Second, the causality-embedded plot lines should be effectively extracted for coherent rewriting. Therefore, two corresponding tactics are proposed: 1) A hallucination-aware refinement method (HAR) to iteratively discover and eliminate the affections of hallucinations; and 2) a causal plot-graph construction method (CPC) based on a greedy cycle-breaking algorithm to efficiently construct plot lines with event causalities. Recruiting those efficient techniques, R$^2$ utilizes two modules to mimic the human screenplay rewriting process: The Reader module adopts a sliding window and CPC to build the causal plot graphs, while the Rewriter module generates first the scene outlines based on the graphs and then the screenplays. HAR is integrated into both modules for accurate inferences of LLMs. Experimental results demonstrate the superiority of R$^2$, which substantially outperforms three existing approaches (51.3%, 22.6%, and 57.1% absolute increases) in pairwise comparison at the overall win rate for GPT-4o.

Yifan Wu, Jiyue Jiang, Xichen Ye et al.

Biological foundation models (BioFMs), pretrained on large-scale biological sequences, have recently shown strong potential in providing meaningful representations for diverse downstream bioinformatics tasks. However, such models often rely on millions to billions of training sequences and billions of parameters, resulting in prohibitive computational costs and significant barriers to reproducibility and accessibility, particularly for academic labs. To address these challenges, we investigate the feasibility of data pruning for BioFM pretraining and propose a post-hoc influence-guided data pruning framework tailored to biological domains. Our approach introduces a subset-based self-influence formulation that enables efficient estimation of sample importance at low computational cost, and builds upon it two simple yet effective selection strategies, namely Top-k Influence (Top I) and Coverage-Centric Influence (CCI). We empirically validate our method on two representative BioFMs, RNA-FM and ESM-C. For RNA, our framework consistently outperforms random selection baselines under an extreme pruning rate of over 99 percent, demonstrating its effectiveness. Furthermore, we show the generalizability of our framework on protein-related tasks using ESM-C. In particular, our coreset even outperforms random subsets that are ten times larger in both RNA and protein settings, revealing substantial redundancy in biological sequence datasets. These findings underscore the potential of influence-guided data pruning to substantially reduce the computational cost of BioFM pretraining, paving the way for more efficient, accessible, and sustainable biological AI research.

Daniel Jason Tan, Jiayang Chen, Dilruk Perera et al.

ICU enteral feeding remains sub-optimal due to limited personalization and uncertainty about appropriate calorie, protein, and fluid targets, particularly under rapidly changing metabolic demands and heterogeneous patient responses. This study introduces DeepEN, a reinforcement learning (RL)-based framework that personalizes enteral nutrition (EN) dosing for critically ill patients using electronic health record data. DeepEN was trained on over 11,000 ICU patients from the MIMIC-IV database to generate 4-hourly, patient-specific targets for caloric, protein, and fluid intake. The model's state space integrates demographics, comorbidities, vital signs, laboratory results, and prior interventions relevant to nutritional management, while its reward function balances short-term physiological and nutrition-related goals with long-term survival. A dueling double deep Q-network with Conservative Q-Learning regularization is used to ensure safe and reliable policy learning from retrospective data. DeepEN achieved a 3.7 $\pm$ 0.17 percentage-point absolute reduction in estimated mortality compared with the clinician policy (18.8% vs 22.5%) and higher expected returns compared with guideline-based dosing (11.89 vs 8.11), with improvements in key nutritional biomarkers. U-shaped associations between deviations from clinician dosing and mortality suggest that the learned policy aligns with high-value clinician actions while diverging from suboptimal ones. These findings demonstrate the feasibility of conservative offline RL for individualized EN therapy and suggest that data-driven personalization may improve outcomes beyond guideline- or heuristic-based approaches.