Zang Zelin, Li Liangyu, Xu Yongjie, Duan Chenrui, Shen Yue, Sun Yi, Lei Zhen, Li Stan Z
Westlake Institute for Advanced Studies, Westlake University, HangZhou, 310000, China.
Centre for Artificial Intelligence and Robotics (CAIR), HKISI-CAS, 310000.
Brief Bioinform. 2025 Jul 2;26(4). doi: 10.1093/bib/bbaf405.
Spatial transcriptomics (ST) technologies have revolutionized the study of gene expression patterns in tissues by providing multimodal data, including transcriptomic (Tra.), spatial, and morphological modalities, thereby offering new opportunities to understand tissue biology beyond traditional Tra. However, we identify the modality bias phenomenon in ST data species, i.e. the inconsistent contribution of different modalities to the labels leads to a tendency for the analysis methods to retain the information of the dominant modality. How to mitigate the adverse effects of modality bias to satisfy various downstream tasks remains a fundamental challenge. This paper introduces Multiple-modality Structure Transformation, named MuST, a novel methodology to tackle the challenge. MuST integrates the multi-modality information contained in the ST data effectively into a uniform latent space to provide a foundation for all the downstream tasks. It learns intrinsic local structures by topology discovery strategy and topology fusion loss function to solve the inconsistencies among different modalities. Thus, these topology-based and deep learning techniques provide a solid foundation for a variety of analytical tasks while coordinating different modalities. The effectiveness of MuST is assessed by performance metrics and biological significance. The results show that it outperforms existing state-of-the-art methods with clear advantages in the precision of identifying and preserving structures of tissues and biomarkers. MuST offers a versatile toolkit for the intricate analysis of complex biological systems.
空间转录组学(ST)技术通过提供多模态数据,包括转录组学(Tra.)、空间和形态学模态,彻底改变了组织中基因表达模式的研究,从而为超越传统转录组学理解组织生物学提供了新机会。然而,我们发现了ST数据物种中的模态偏差现象,即不同模态对标签的贡献不一致,导致分析方法倾向于保留主导模态的信息。如何减轻模态偏差的不利影响以满足各种下游任务仍然是一个基本挑战。本文介绍了一种名为多模态结构转换(MuST)的新方法来应对这一挑战。MuST将ST数据中包含的多模态信息有效地整合到一个统一的潜在空间中,为所有下游任务提供基础。它通过拓扑发现策略和拓扑融合损失函数学习内在局部结构,以解决不同模态之间的不一致性。因此,这些基于拓扑和深度学习的技术在协调不同模态的同时,为各种分析任务提供了坚实基础。通过性能指标和生物学意义评估了MuST的有效性。结果表明,它在识别和保留组织及生物标志物结构的精度方面明显优于现有最先进方法。MuST为复杂生物系统的复杂分析提供了一个多功能工具包。
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