融合组织形态与基因表达,提升空间转录组域边界解析精度
MultiST: A Cross-Attention-Based Multimodal Model for Spatial Transcriptomic
- 通过跨注意力机制联合建模基因表达、空间拓扑与组织形态
- 在13个数据集上实现更清晰的域边界和更稳定的伪时序轨迹
- 适合研究组织结构与细胞互作的生物学家及计算医学团队
空间转录组学(ST)可在保留组织空间信息的前提下进行全基因组分析,为原位研究组织结构与细胞间互作提供了前所未有的机遇。尽管近期取得进展,现有方法常缺乏对组织形态与分子谱型的有效整合,依赖浅层融合或完全忽略组织图像,限制了对模糊空间域边界的解析能力。为此,我们提出MultiST,一种统一的多模态框架,通过基于交叉注意力的融合方式联合建模空间拓扑、基因表达与组织形态。MultiST采用图神经网络基因编码器结合对抗性对齐,学习鲁棒的空间表征,并整合经过颜色归一化的组织特征,以捕捉分子与形态之间的依赖关系并优化域边界。我们在涵盖两个器官的13个多样化ST数据集上评估该方法,包括人脑皮层和乳腺癌组织。结果表明,MultiST生成的空间域边界更清晰、更连贯,带来了更稳定的伪时序轨迹和更具生物学意义的细胞互作模式。MultiST框架及源代码已开源:https://github.com/LabJunBMI/MultiST.git。
原文摘要 · Abstract (English)
Spatial transcriptomics (ST) enables transcriptome-wide profiling while preserving the spatial context of tissues, offering unprecedented opportunities to study tissue organization and cell-cell interactions in situ. Despite recent advances, existing methods often lack effective integration of histological morphology with molecular profiles, relying on shallow fusion strategies or omitting tissue images altogether, which limits their ability to resolve ambiguous spatial domain boundaries. To address this challenge, we propose MultiST, a unified multimodal framework that jointly models spatial topology, gene expression, and tissue morphology through cross-attention-based fusion. MultiST employs graph-based gene encoders with adversarial alignment to learn robust spatial representations, while integrating color-normalized histological features to capture molecular-morphological dependencies and refine domain boundaries. We evaluated the proposed method on 13 diverse ST datasets spanning two organs, including human brain cortex and breast cancer tissue. MultiST yields spatial domains with clearer and more coherent boundaries than existing methods, leading to more stable pseudotime trajectories and more biologically interpretable cell-cell interaction patterns. The MultiST framework and source code are available at https://github.com/LabJunBMI/MultiST.git.
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