arXiv:2602.22236q-bio.GNcs.CV2026-02被引 1

用状态空间模型动态融合多模态生物序列,提升RNA相互作用预测精度。

CrossLLM-Mamba: Multimodal State Space Fusion of LLMs for RNA Interaction Prediction

  • 通过双向Mamba编码器实现跨模态嵌入的动态交互
  • 在RPI1460上达到0.892的MCC,比之前最佳提升5.2%
  • 适合需要高精度生物分子互作预测的研究者

准确预测与RNA相关的相互作用对于理解细胞调控和推动药物发现至关重要。尽管生物大语言模型(BioLLMs)如ESM-2和RiNALMo提供了强大的序列表征,现有方法依赖静态融合策略,无法捕捉分子结合的动态和上下文依赖特性。我们提出CrossLLM-Mamba,将互作预测重构为状态空间对齐问题。通过双向Mamba编码器,该方法利用隐藏状态传播实现模态间深度“交叉对话”,将互作建模为动态序列转换而非静态特征重叠。框架保持线性计算复杂度,可扩展至高维BioLLM嵌入。我们进一步引入高斯噪声注入和焦点损失,增强对难负样本的鲁棒性。在三种互作类型(RNA-蛋白、RNA-小分子、RNA-RNA)上的全面实验表明,CrossLLM-Mamba表现达到当前最优水平。在RPI1460基准上,模型取得0.892的MCC,优于前人最佳结果5.2%;在结合亲和力预测中,于核糖开关和重复RNA子类型上达到超过0.95的皮尔逊相关系数。这些结果确立了状态空间建模在多模态生物互作预测中的强大潜力。

原文摘要 · Abstract (English)

Accurate prediction of RNA-associated interactions is essential for understanding cellular regulation and advancing drug discovery. While Biological Large Language Models (BioLLMs) such as ESM-2 and RiNALMo provide powerful sequence representations, existing methods rely on static fusion strategies that fail to capture the dynamic, context-dependent nature of molecular binding. We introduce CrossLLM-Mamba, a novel framework that reformulates interaction prediction as a state-space alignment problem. By leveraging bidirectional Mamba encoders, our approach enables deep ``crosstalk'' between modality-specific embeddings through hidden state propagation, modeling interactions as dynamic sequence transitions rather than static feature overlaps. The framework maintains linear computational complexity, making it scalable to high-dimensional BioLLM embeddings. We further incorporate Gaussian noise injection and Focal Loss to enhance robustness against hard-negative samples. Comprehensive experiments across three interaction categories, RNA-protein, RNA-small molecule, and RNA-RNA demonstrate that CrossLLM-Mamba achieves state-of-the-art performance. On the RPI1460 benchmark, our model attains an MCC of 0.892, surpassing the previous best by 5.2\%. For binding affinity prediction, we achieve Pearson correlations exceeding 0.95 on riboswitch and repeat RNA subtypes. These results establish state-space modeling as a powerful paradigm for multi-modal biological interaction prediction.

RNA预测多模态学习状态空间模型

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