基于空间转录组学数据估算肿瘤中的细胞谱系。

Estimation of cell lineages in tumors from spatial transcriptomics data.

机构信息

Cancer Data Science Lab, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

出版信息

Nat Commun. 2023 Feb 2;14(1):568. doi: 10.1038/s41467-023-36062-6.

Abstract

Spatial transcriptomics (ST) technology through in situ capturing has enabled topographical gene expression profiling of tumor tissues. However, each capturing spot may contain diverse immune and malignant cells, with different cell densities across tissue regions. Cell type deconvolution in tumor ST data remains challenging for existing methods designed to decompose general ST or bulk tumor data. We develop the Spatial Cellular Estimator for Tumors (SpaCET) to infer cell identities from tumor ST data. SpaCET first estimates cancer cell abundance by integrating a gene pattern dictionary of copy number alterations and expression changes in common malignancies. A constrained regression model then calibrates local cell densities and determines immune and stromal cell lineage fractions. SpaCET provides higher accuracy than existing methods based on simulation and real ST data with matched double-blind histopathology annotations as ground truth. Further, coupling cell fractions with ligand-receptor coexpression analysis, SpaCET reveals how intercellular interactions at the tumor-immune interface promote cancer progression.

摘要

空间转录组学(ST)技术通过原位捕获,实现了肿瘤组织的基因表达图谱分析。然而,每个捕获点可能包含不同的免疫细胞和恶性细胞,不同的细胞密度分布在组织区域。对于现有的旨在分解一般 ST 或批量肿瘤数据的方法来说,肿瘤 ST 数据中的细胞类型去卷积仍然具有挑战性。我们开发了用于肿瘤的空间细胞估计器(SpaCET),以从肿瘤 ST 数据中推断细胞身份。SpaCET 首先通过整合常见恶性肿瘤中拷贝数改变和表达变化的基因模式字典来估计癌细胞丰度。然后,一个约束回归模型对局部细胞密度进行校准,并确定免疫细胞和基质细胞谱系分数。基于模拟和具有匹配双盲组织病理学注释的真实 ST 数据的准确性评估表明,SpaCET 比现有的方法具有更高的准确性。此外,将细胞分数与配体-受体共表达分析相结合,SpaCET 揭示了肿瘤免疫界面的细胞间相互作用如何促进癌症进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069b/9895078/87df14377778/41467_2023_36062_Fig1_HTML.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索