arXiv:2604.24506cs.AIcs.LG2026-04

MIMIC可跨模态生成和修复生物分子,实现精准设计与预测。

MIMIC: A Generative Multimodal Foundation Model for Biomolecules

论文配图:MIMIC: A Generative Multimodal Foundation Model for Biomolecules
图 1 · 摘自论文原文
  • 分轨架构支持任意模态组合推理,重建缺失分子信息。
  • 在剪接预测上达最新水平,能识别临床相关突变的修复编辑。
  • 适合需多模态协同设计的生物医药研究者使用。

生物功能由序列、结构、调控、进化及细胞环境等多维度耦合约束形成,但现有生物领域基础模型多局限于单一模态或固定任务。我们提出MIMIC,一个基于新构建对齐数据集LORE的生成式多模态基础模型,整合核酸、蛋白质、进化、结构、调控及语义上下文模态,覆盖基因组、转录组与蛋白质组部分观测分子状态。MIMIC采用分轨编码器-解码器架构,可基于任意观测模态子集,重建或生成缺失分子成分。多模态条件显著提升序列重建性能,其学习表征在RNA与蛋白下游任务中达领先水平。在剪接预测中表现最优,联合生成框架支持等位基因感知推断,进一步提升效果。除预测外,该生成框架还支持受控设计:针对临床相关的HBB剪接突变,仅利用进化与结构信号识别修正编辑而不完全逆转;对PD-L1和hACE2结合位点,联合形状与表面化学条件生成多样且高置信度的目标结合序列。此外,实验上下文作为语义条件输入,实现对依赖实验的RNA化学探测建模,而非将其视为固定输出。这些结果表明,MIMIC的多模态生成建模为统一表示学习、条件预测与受限生物分子设计提供了强大基础。

原文摘要 · Abstract (English)

Biological function emerges from coupled constraints across sequence, structure, regulation, evolution, and cellular context, yet most foundation models in biology are trained within one modality or for a fixed forward task. We present MIMIC, a generative multimodal foundation model trained on our newly curated and aligned dataset, LORE, linking nucleic acid, protein, evolutionary, structural, regulatory, and semantic/contextual modalities within partially observed biomolecular states. MIMIC uses a split-track encoder-decoder architecture to condition on arbitrary subsets of observed modalities and reconstruct or generate missing components of molecular state across the genome, transcriptome, and proteome. Multimodal conditioning consistently improves MIMIC's sequence reconstruction relative to sequence-only inputs, while its learned representations enable state-of-the-art performance on RNA and protein downstream tasks. MIMIC achieves state-of-the-art splicing prediction, and its joint generative formulation enables isoform-aware inference that further improves performance. Beyond prediction, the same generative framework supports constrained design. For RNA, MIMIC identifies corrective edits in a clinically relevant HBB splice-disrupting mutation without reverting it by using evolutionary and structural signals. For proteins, jointly conditioning on shape and surface chemistry of PD-L1 and hACE2 binding sites produces diverse, high-confidence sequences with strong in silico support for target binding. Finally, MIMIC uses experimental context as semantic conditioning to model assay-dependent RNA chemical probing, rather than treating context as a fixed output. Together, these results position MIMIC's aligned multimodal generative modeling as a strong foundation for unifying representation learning, conditional prediction, and constrained biomolecular design within a single model.

多模态生物分子生成模型药物设计

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