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STMGraph:通过双掩码动态图注意力模型实现转录组的空间上下文感知

STMGraph: spatial-context-aware of transcriptomes via a dual-remasked dynamic graph attention model.

作者信息

Lin Lixian, Wang Haoyu, Chen Yuxiao, Wang Yuanyuan, Xu Yujie, Chen Zhenglin, Yang Yuemin, Liu Kunpeng, Ma Xiaokai

机构信息

Center for Genomics and Biotechnology, Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Haixia Institute of Science and Technology, Fujian Agriculture and Forestry University, No. 15 Shangxiadian Road, Cangshan District, Fuzhou 350002, China.

College of Life Science, Fujian Agriculture and Forestry University, No. 15 Shangxiadian Road, Cangshan District, Fuzhou 350002, China.

出版信息

Brief Bioinform. 2024 Nov 22;26(1). doi: 10.1093/bib/bbae685.

DOI:10.1093/bib/bbae685
PMID:39764614
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11704419/
Abstract

Spatial transcriptomics (ST) technologies enable dissecting the tissue architecture in spatial context. To perceive the global contextual information of gene expression patterns in tissue, the spatial dependence of cells must be fully considered by integrating both local and non-local features by means of spatial-context-aware. However, the current ST integration algorithm ignores for ST dropouts, which impedes the spatial-aware of ST features, resulting in challenges in the accuracy and robustness of microenvironmental heterogeneity detecting, spatial domain clustering, and batch-effects correction. Here, we developed an STMGraph, a universal dual-view dynamic deep learning framework that combines dual-remask (MASK-REMASK) with dynamic graph attention model (DGAT) to exploit ST data outperforming pre-existing tools. The dual-remask mechanism masks the embeddings before encoding and decoding, establishing dual-decoding-view to share features mutually. DGAT leverages self-supervision to update graph linkage relationships from two distinct perspectives, thereby generating a comprehensive representation for each node. Systematic benchmarking against 10 state-of-the-art tools revealed that the STMGraph has the optimal performance with high accuracy and robustness on spatial domain clustering for the datasets of diverse ST platforms from multi- to sub-cellular resolutions. Furthermore, STMGraph aggregates ST information cross regions by dual-remask to realize the batch-effects correction implicitly, allowing for spatial domain clustering of ST multi-slices. STMGraph is platform independent and superior in spatial-context-aware to achieve microenvironmental heterogeneity detection, spatial domain clustering, batch-effects correction, and new biological discovery, and is therefore a desirable novel tool for diverse ST studies.

摘要

空间转录组学(ST)技术能够在空间背景下剖析组织结构。为了感知组织中基因表达模式的全局上下文信息,必须通过空间上下文感知来整合局部和非局部特征,充分考虑细胞的空间依赖性。然而,当前的ST整合算法忽略了ST缺失值,这阻碍了对ST特征的空间感知,导致在微环境异质性检测、空间域聚类和批次效应校正的准确性和稳健性方面面临挑战。在此,我们开发了STMGraph,这是一个通用的双视图动态深度学习框架,它将双重掩码(MASK - REMASK)与动态图注意力模型(DGAT)相结合,以利用ST数据,性能优于现有工具。双重掩码机制在编码和解码之前对嵌入进行掩码处理,建立双解码视图以相互共享特征。DGAT利用自监督从两个不同的角度更新图链接关系,从而为每个节点生成全面的表示。与10种先进工具进行的系统基准测试表明,STMGraph在从多细胞到亚细胞分辨率的不同ST平台数据集的空间域聚类方面具有高精度和稳健性的最佳性能。此外,STMGraph通过双重掩码跨区域聚合ST信息,以隐式实现批次效应校正,从而允许对ST多切片进行空间域聚类。STMGraph是平台独立的,在空间上下文感知方面表现出色,能够实现微环境异质性检测、空间域聚类、批次效应校正和新的生物学发现,因此是各种ST研究中理想的新型工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd5d/11704419/325d26986984/bbae685f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd5d/11704419/349a7c5fd4ef/bbae685f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd5d/11704419/7a5376ea9a77/bbae685f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd5d/11704419/ed5941374fe6/bbae685f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd5d/11704419/ba9e9b7eece3/bbae685f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd5d/11704419/325d26986984/bbae685f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd5d/11704419/349a7c5fd4ef/bbae685f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd5d/11704419/754601ef373d/bbae685f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd5d/11704419/7a5376ea9a77/bbae685f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd5d/11704419/ed5941374fe6/bbae685f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd5d/11704419/ba9e9b7eece3/bbae685f5.jpg
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本文引用的文献

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Deciphering spatial domains from spatial multi-omics with SpatialGlue.利用 SpatialGlue 从空间多组学中破译空间域。
Nat Methods. 2024 Sep;21(9):1658-1667. doi: 10.1038/s41592-024-02316-4. Epub 2024 Jun 21.
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High-density generation of spatial transcriptomics with STAGE.利用 STAGE 进行空间转录组学的高密度生成。
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EAGS: efficient and adaptive Gaussian smoothing applied to high-resolved spatial transcriptomics.EAGS:应用于高分辨率空间转录组学的高效自适应高斯平滑
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Genome Med. 2024 Jan 12;16(1):12. doi: 10.1186/s13073-024-01283-x.
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Mutations in Structural Genes of the Mitochondrial Complex IV May Influence Breast Cancer.线粒体复合物 IV 的结构基因突变可能影响乳腺癌。
Genes (Basel). 2023 Jul 18;14(7):1465. doi: 10.3390/genes14071465.
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Spatial-MGCN: a novel multi-view graph convolutional network for identifying spatial domains with attention mechanism.空间-MGCN:一种新颖的多视图图卷积网络,用于通过注意力机制识别空间域。
Brief Bioinform. 2023 Sep 20;24(5). doi: 10.1093/bib/bbad262.
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Spatially informed clustering, integration, and deconvolution of spatial transcriptomics with GraphST.基于 GraphST 的空间转录组学的空间信息聚类、整合和解卷积
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STEEL enables high-resolution delineation of spatiotemporal transcriptomic data.STEEL能够对时空转录组数据进行高分辨率描绘。
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