美国圣地亚哥科学研究所Peter V. Kharchenko和美国加州大学Chun Jimmie Ye共同合作，近期取得重要工作进展。他们提出了通过张量分解法揭示使患者群体分层的多细胞转录变异协调模式。相关研究成果2024年9月23日在线发表于《自然—生物技术》杂志上。

据介绍，组织水平和生物体水平的生物过程通常涉及多种不同细胞类型的协调作用。最近将单细胞检测应用于许多个体，应该能够研究一种细胞类型的供体水平变异如何与其他细胞类型的变异联系起来。

研究人员介绍了一种称为单细胞可解释张量分解（scITD）的计算方法，通过考虑多种细胞类型的联合表达变化，来识别个体间变异的共同轴。scITD将每种细胞类型的表达矩阵组合成高阶矩阵，并使用Tucker张量分解对结果进行因子分解。

将scITD应用于115名狼疮患者和83名2019冠状病毒病患者的单细胞RNA测序数据，研究人员确定了与疾病严重程度和特定表型（如狼疮肾炎）相关的协调细胞活动模式。scITD结果还暗示了可能介导细胞类型之间协调的特定信号通路。

总之，scITD提供了一种理解个体间细胞状态协变的工具，可以深入了解定义和分层疾病的复杂过程。

附：英文原文

Title: Coordinated, multicellular patterns of transcriptional variation that stratify patient cohorts are revealed by tensor decomposition

Author: Mitchel, Jonathan, Gordon, M. Grace, Perez, Richard K., Biederstedt, Evan, Bueno, Raymund, Ye, Chun Jimmie, Kharchenko, Peter V.

Issue&Volume: 2024-09-23

Abstract: Tissue-level and organism-level biological processes often involve the coordinated action of multiple distinct cell types. The recent application of single-cell assays to many individuals should enable the study of how donor-level variation in one cell type is linked to that in other cell types. Here we introduce a computational approach called single-cell interpretable tensor decomposition (scITD) to identify common axes of interindividual variation by considering joint expression variation across multiple cell types. scITD combines expression matrices from each cell type into a higher-order matrix and factorizes the result using the Tucker tensor decomposition. Applying scITD to single-cell RNA-sequencing data on 115 persons with lupus and 83 persons with coronavirus disease 2019, we identify patterns of coordinated cellular activity linked to disease severity and specific phenotypes, such as lupus nephritis. scITD results also implicate specific signaling pathways likely mediating coordination between cell types. Overall, scITD offers a tool for understanding the covariation of cell states across individuals, which can yield insights into the complex processes that define and stratify disease.

DOI: 10.1038/s41587-024-02411-z

Source: https://www.nature.com/articles/s41587-024-02411-z