融合多模态信息,提升虚拟细胞基因扰动预测的准确性与可解释性。
AROMA: Augmented Reasoning Over a Multimodal Architecture for Virtual Cell Genetic Perturbation Modeling

- 结合文本、图拓扑和蛋白序列,构建多模态推理框架。
- 在498,000+样本上训练,零样本迁移仍保持鲁棒性。
- 适合生物机制研究者,助力可解释的基因扰动建模。
虚拟细胞建模可预测基因扰动下的分子状态变化,对生物机制研究至关重要。现有方法存在推理无约束、预测不可解释、检索信号与调控拓扑弱对齐等问题。为此,我们提出AROMA:一种基于多模态架构的增强推理模型,融合文本证据、图拓扑信息与蛋白序列特征,建模扰动-靶点依赖关系,并采用两阶段优化策略,使预测兼具准确性和可解释性。我们还构建了两个知识图谱及包含超过498,000个样本的扰动推理数据集PerturbReason,作为可复用资源。实验表明,AROMA在多个细胞系中优于现有方法,在未见细胞系的零样本评估以及知识稀疏、长尾场景下均表现稳健。结果表明,结合知识驱动的多模态建模与证据检索,是实现更可靠、可解释虚拟细胞扰动预测的可行路径。模型权重见https://huggingface.co/blazerye/AROMA,代码见https://github.com/blazerye/AROMA。
原文摘要 · Abstract (English)
Virtual cell modeling predicts molecular state changes under genetic perturbations in silico, which is essential for biological mechanism studies. However, existing approaches suffer from unconstrained reasoning, uninterpretable predictions, and retrieval signals that are weakly aligned with regulatory topology. To address these limitations, we propose AROMA, an Augmented Reasoning Over a Multimodal Architecture for virtual cell genetic perturbation modeling. AROMA integrates textual evidence, graph-topology information, and protein sequence features to model perturbation-target dependencies, and is trained with a two-stage optimization strategy to yield predictions that are both accurate and interpretable. We also construct two knowledge graphs and a perturbation reasoning dataset, PerturbReason, containing more than 498k samples, as reusable resources for the virtual cell domain. Experiments show that AROMA outperforms existing methods across multiple cell lines, and remains robust under zero-shot evaluation on an unseen cell line, as well as in knowledge-sparse, long-tail scenarios. Overall, AROMA demonstrates that combining knowledge-driven multimodal modeling with evidence retrieval provides a promising pathway toward more reliable and interpretable virtual cell perturbation prediction. Model weights are available at https://huggingface.co/blazerye/AROMA. Code is available at https://github.com/blazerye/AROMA.
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