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Path-MGCN: a pathway activity-based multi-view graph convolutional network for determining spatial domains

delete2025-07-01
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OA
AI
Q
Qirui Zhou
C
Chaowen Li
陈
陈超 (Chao Chen)
S
Songqing Gu
W
Weijun Sun
Z
Zongmeng Zhang
Y
Yishan Cai
Y
Yonghui Huang
H
Hongtao Liu
C
Chao Yang
X
Xin Chen *
DOI:10.1093/bib/bbaf365delete
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摘要

摘要

En 中文
空间转录组学(ST)能够全面测量基因表达谱,同时保留空间信息。为识别空间域(ST数据分析的基本任务之一,用于理解组织架构),已提出多种累积的计算框架。然而,当前方法常忽视通路层面的功能背景,并难以处理数据稀疏性问题。因此,我们开发了Path-MGCN,一种具有注意力机制的多视图图卷积网络(GCN),该网络整合了通路信息。我们首先通过基因集变异性分析从基因表达计算位点层面的通路活性得分,并构建分别表示空间接近度和功能接近度的不同邻接图。多视图GCN学习空间、通路及共享嵌入,这些嵌入通过注意力机制自适应融合,随后由零膨胀负二项式解码器保留原始转录组信息。在多种数据集(人背外侧前额叶皮层、乳腺癌及小鼠脑组织)不同分辨率下的全面评估表明,Path-MGCN具有卓越的准确性和稳健性,显著优于当前先进方法,并在不同通路数据库(京都基因与基因组百科全书、基因本体论、Reactome)中均保持高性能。关键在于,Path-MGCN增强了生物学可解释性,能够识别类三级淋巴样结构区域,以及与人乳腺癌肿瘤进展阶段相关的空间分辨代谢异质性(如缺氧、糖酵解、AMP激活蛋白激酶信号通路)。通过有效整合功能背景,Path-MGCN推动了ST分析的发展,提供了一个准确且可解释的框架以剖析组织异质性,并实现分子通路的空间精细绘制,凸显了开发安全高效协同抗肿瘤疗法的关键靶向治疗策略。
Keyword:
pathway
spatial transcriptomics
multi-view graph convolutional network
attention mechanism
spatial domain
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Briefings in Bioinformatics 封面图
Briefings in Bioinformatics
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Guangdong University of Technology
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被引数: 3.1W
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Guangdong Polytechnic Normal University
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