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跨异质空间样本的细胞状态的多尺度和多上下文可解释映射。

Multi-scale and multi-context interpretable mapping of cell states across heterogeneous spatial samples.

作者信息

Martin Patrick C N, Wang Wenqi, Kim Hyobin, Holze Henrietta, Fisher Paul B, Saavedra Arturo P, Winn Robert A, Madan Esha, Gogna Rajan, Won Kyoung Jae

机构信息

Department of Computational Biomedicine, Cedars-Sinai Medical Center, Hollywood, CA, USA.

Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.

出版信息

Nat Commun. 2025 Aug 21;16(1):7814. doi: 10.1038/s41467-025-62782-y.


DOI:10.1038/s41467-025-62782-y
PMID:40841370
Abstract

There is a growing demand for methods that can effectively align and compare spatial data in the absence of obvious visual correspondence. To address this challenge, we developed an interpretable cell mapping strategy based on solving a Linear Assignment Problem (LAP) where the total cost is computed by considering cells and their niches. We demonstrate that our approach outperforms other methods at capturing the spatial context of cells in synthetic and real data sets. The flexibility of our implementation enhances the interpretability of mapping and allows for accurate cell mapping across samples, technologies, resolutions, developmental and regenerative time. We show spatiotemporal decoupling of cells during development and patient level sub-populations in In Situ Mass Cytometry (IMC) cancer data sets. Our interpretable mapping approach facilitates systemic comparison and analysis of heterogeneous spatial data. We provide a flexible framework for researchers to tailor their analysis to the specific biological and research context.

摘要

对于能够在缺乏明显视觉对应关系的情况下有效对齐和比较空间数据的方法,需求日益增长。为应对这一挑战,我们基于解决线性分配问题(LAP)开发了一种可解释的细胞映射策略,其中总成本通过考虑细胞及其生态位来计算。我们证明,在捕获合成数据集和真实数据集中细胞的空间背景方面,我们的方法优于其他方法。我们实现方式的灵活性增强了映射的可解释性,并允许在样本、技术、分辨率、发育和再生时间之间进行准确的细胞映射。我们展示了发育过程中细胞的时空解耦以及原位质谱流式细胞术(IMC)癌症数据集中患者水平的亚群。我们的可解释映射方法有助于对异质空间数据进行系统的比较和分析。我们为研究人员提供了一个灵活的框架,使他们能够根据特定的生物学和研究背景调整分析。

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本文引用的文献

[1]
Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells.

Nat Biotechnol. 2024-12-9

[2]
Data enhancement in the age of spatial biology.

Adv Cancer Res. 2024

[3]
High resolution mapping of the tumor microenvironment using integrated single-cell, spatial and in situ analysis.

Nat Commun. 2023-12-19

[4]
STalign: Alignment of spatial transcriptomics data using diffeomorphic metric mapping.

Nat Commun. 2023-12-8

[5]
Spatial-linked alignment tool (SLAT) for aligning heterogenous slices.

Nat Commun. 2023-11-9

[6]
CellNeighborEX: deciphering neighbor-dependent gene expression from spatial transcriptomics data.

Mol Syst Biol. 2023-11-9

[7]
Alignment of spatial genomics data using deep Gaussian processes.

Nat Methods. 2023-9

[8]
Targeting Cellular Retinoic Acid Binding Protein 1 with Retinoic Acid-like Compounds to Mitigate Motor Neuron Degeneration.

Int J Mol Sci. 2023-3-4

[9]
High-resolution alignment of single-cell and spatial transcriptomes with CytoSPACE.

Nat Biotechnol. 2023-11

[10]
Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses.

Nat Commun. 2023-2-7

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