Spatially aware dimension reduction for spatial transcriptomics.

Spatially aware dimension reduction for spatial transcriptomics.
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空间转录组学的空间感知降维。

DOI:
10.1038/s41467-022-34879-1
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发表时间:
2022-11-23
影响因子:
16.6
通讯作者:
Zhou, Xiang
Zhou, Xiang
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Shang, Lulu;Zhou, Xiang

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空间转录组学是一组基因组技术的集合,这些技术使具有空间定位信息的组织的转录组谱成为可能。分析空间转录数据在计算上具有挑战性,因为从各种空间转录技术收集的数据往往具有噪声,并且显示出组织位置之间的大量空间相关性。在这里,我们开发了一种空间感知降维方法SpatialPCA,该方法可以提取包含生物信号的空间转录数据的低维表示,并保留空间相关结构,从而释放了以前在单细胞RNAseq研究中开发的许多现有计算工具,用于空间转录数据的定制分析。我们说明了空间主成分分析在空间域检测中的优点,并探索了其在组织轨迹推断和高分辨率空间地图构建中的应用。在实际的数据应用中,SpatialPCA在检测到的肿瘤周围微环境中识别关键的分子和免疫学特征,包括在肿瘤发生和转移过程中塑造逐渐转录转换的第三级淋巴结构。此外,SpatialPCA检测过去的神经元发育历史,这是目前大脑皮质组织位置转录图景的基础。空间转录分析可能会受到噪声和跨组织位置的空间相关性的影响。在这里,作者发展了SpatialPCA,这是一种空间感知的降维方法,显式地建模空间相关结构,并展示了它在健康和肿瘤组织分析中的应用。
Spatial transcriptomics are a collection of genomic technologies that have enabled transcriptomic profiling on tissues with spatial localization information. Analyzing spatial transcriptomic data is computationally challenging, as the data collected from various spatial transcriptomic technologies are often noisy and display substantial spatial correlation across tissue locations. Here, we develop a spatially-aware dimension reduction method, SpatialPCA, that can extract a low dimensional representation of the spatial transcriptomics data with biological signal and preserved spatial correlation structure, thus unlocking many existing computational tools previously developed in single-cell RNAseq studies for tailored analysis of spatial transcriptomics. We illustrate the benefits of SpatialPCA for spatial domain detection and explores its utility for trajectory inference on the tissue and for high-resolution spatial map construction. In the real data applications, SpatialPCA identifies key molecular and immunological signatures in a detected tumor surrounding microenvironment, including a tertiary lymphoid structure that shapes the gradual transcriptomic transition during tumorigenesis and metastasis. In addition, SpatialPCA detects the past neuronal developmental history that underlies the current transcriptomic landscape across tissue locations in the cortex. Spatial transcriptomics analyses can be affected by noise and spatial correlation across tissue locations. Here, the authors develop SpatialPCA, a spatially-aware dimensionality reduction method that explicitly models spatial correlation structures, and show its application to the analysis of healthy and tumour tissues.
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