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CITEMO:一种灵活的单细胞多组学分析框架,用于揭示免疫细胞的异质性。

CITEMO: A flexible single-cell multimodal omics analysis framework to reveal the heterogeneity of immune cells.

机构信息

Department of Physics, And Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China.

National Institute for Data Science in Health and Medicine, and State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, Xiamen University, Xiamen, China.

出版信息

RNA Biol. 2022 Jan;19(1):290-304. doi: 10.1080/15476286.2022.2027151.


DOI:10.1080/15476286.2022.2027151
PMID:35130112
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8824218/
Abstract

Simultaneous measurement of multiple modalities in single-cell analysis, represented by CITE-seq, is a promising approach to link transcriptional changes to cellular phenotype and function, requiring new computational methods to define cellular subtypes and states based on multiple data types. Here, we design a flexible single-cell multimodal analysis framework, called CITEMO, to integrate the transcriptome and antibody-derived tags (ADT) data to capture cell heterogeneity from the multi omics perspective. CITEMO uses Principal Component Analysis (PCA) to obtain a low-dimensional representation of the transcriptome and ADT, respectively, and then employs PCA again to integrate these low-dimensional multimodal data for downstream analysis. To investigate the effectiveness of the CITEMO framework, we apply CITEMO to analyse the cell subtypes of Cord Blood Mononuclear Cells (CBMC) samples. Results show that the CITEMO framework can comprehensively analyse single-cell multimodal samples and accurately identify cell subtypes. Besides, we find some specific immune cells that co-express multiple ADT markers. To better describe the co-expression phenomenon, we introduce the co-expression entropy to measure the heterogeneous distribution of the ADT combinations. To further validate the robustness of the CITEMO framework, we analyse Human Bone Marrow Cell (HBMC) samples and identify different states of the same cell type. CITEMO has an excellent performance in identifying cell subtypes and states for multimodal omics data. We suggest that the flexible design idea of CITEMO can be an inspiration for other single-cell multimodal tasks. The complete source code and dataset of the CITEMO framework can be obtained from https://github.com/studentiz/CITEMO.

摘要

单细胞分析中多种模式的同步测量,以 CITE-seq 为代表,是一种将转录变化与细胞表型和功能联系起来的有前途的方法,需要新的计算方法来基于多种数据类型定义细胞亚型和状态。在这里,我们设计了一种灵活的单细胞多模态分析框架,称为 CITEMO,用于整合转录组和抗体衍生标签 (ADT) 数据,从多组学的角度捕捉细胞异质性。CITEMO 使用主成分分析 (PCA) 分别获得转录组和 ADT 的低维表示,然后再次使用 PCA 来整合这些低维多模态数据进行下游分析。为了研究 CITEMO 框架的有效性,我们将 CITEMO 应用于分析脐带血单核细胞 (CBMC) 样本的细胞亚型。结果表明,CITEMO 框架可以全面分析单细胞多模态样本并准确识别细胞亚型。此外,我们发现一些特定的免疫细胞共同表达多种 ADT 标记物。为了更好地描述共表达现象,我们引入共表达熵来衡量 ADT 组合的异质分布。为了进一步验证 CITEMO 框架的稳健性,我们分析了人类骨髓细胞 (HBMC) 样本并识别了同一细胞类型的不同状态。CITEMO 在识别多组学数据的细胞亚型和状态方面表现出色。我们建议 CITEMO 的灵活设计理念可以为其他单细胞多模态任务提供启示。CITEMO 框架的完整源代码和数据集可从 https://github.com/studentiz/CITEMO 获得。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d597/8824218/cfe7cdafe306/KRNB_A_2027151_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d597/8824218/dc66d031e5a6/KRNB_A_2027151_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d597/8824218/e7de5f3bccf4/KRNB_A_2027151_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d597/8824218/dd0c5b4ba369/KRNB_A_2027151_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d597/8824218/7bf7184367af/KRNB_A_2027151_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d597/8824218/cfe7cdafe306/KRNB_A_2027151_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d597/8824218/dc66d031e5a6/KRNB_A_2027151_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d597/8824218/e7de5f3bccf4/KRNB_A_2027151_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d597/8824218/dd0c5b4ba369/KRNB_A_2027151_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d597/8824218/7bf7184367af/KRNB_A_2027151_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d597/8824218/cfe7cdafe306/KRNB_A_2027151_F0005_OC.jpg

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引用本文的文献

[1]
Clustering single-cell multi-omics data via graph regularized multi-view ensemble learning.

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[2]
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[4]
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本文引用的文献

[1]
Inference of Gene Regulatory Network from Single-Cell Transcriptomic Data Using pySCENIC.

Methods Mol Biol. 2021

[2]
Integrated analysis of multimodal single-cell data.

Cell. 2021-6-24

[3]
Interpretation of T cell states from single-cell transcriptomics data using reference atlases.

Nat Commun. 2021-5-20

[4]
Intratumor Regulatory Noncytotoxic NK Cells in Patients with Hepatocellular Carcinoma.

Cells. 2021-3-10

[5]
Single-Cell Deconvolution of Head and Neck Squamous Cell Carcinoma.

Cancers (Basel). 2021-3-11

[6]
Terminally Differentiated CD4 T Cells Promote Myocardial Inflammaging.

Front Immunol. 2021

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Single-cell transcriptomic analysis of mIHC images via antigen mapping.

Sci Adv. 2021-3

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Single-cell RNA sequencing: one step closer to the clinic.

Nat Med. 2021-3

[9]
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Bio Protoc. 2020-12-5

[10]
Blinatumomab-induced T cell activation at single cell transcriptome resolution.

BMC Genomics. 2021-3-1

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