Integrated analysis of multimodal single-cell data.

Integrated analysis of multimodal single-cell data.
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多模态单细胞数据的整合分析。

DOI:
10.1016/j.cell.2021.04.048
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发表时间:
2021-06-24
期刊:
影响因子:
64.5
通讯作者:
Satija R
Satija R
中科院分区:
生物学1区
文献类型:
--
作者:
Hao Y;Hao S;Andersen-Nissen E;Mauck WM 3rd;Zheng S;Butler A;Lee MJ;Wilk AJ;Darby C;Zager M;Hoffman P;Stoeckius M;Papalexi E;Mimitou EP;Jain J;Srivastava A;Stuart T;Fleming LM;Yeung B;Rogers AJ;McElrath JM;Blish CA;Gottardo R;Smibert P;Satija R

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多个模式的同时测量代表了单细胞基因组学的一个令人兴奋的前沿,并需要能够基于多模式数据定义细胞状态的计算方法。在这里,我们引入了“加权最近邻”分析,这是一种非监督框架,可以了解每个单元中每种数据类型的相对效用,从而实现对多种模式的综合分析。我们将我们的程序应用于包含211,000个人类外周血单核细胞(PBMC)的CITE-SEQ数据集,其面板延伸到228个抗体,以构建循环免疫系统的多模式参考图谱。多模式分析大大提高了我们解析细胞状态的能力,使我们能够识别和验证以前未报道的淋巴亚群。此外,我们还演示了如何利用这一参考来快速映射新的数据集,并解释对疫苗接种和冠状病毒疾病2019年的免疫反应(新冠肺炎)。我们的方法代表了一种广泛适用的策略,用于分析单细胞多模式数据集,并超越转录组,着眼于细胞身份的统一和多模式定义。“加权最近邻”分析集成了多模式单细胞数据循环人体免疫系统的多模式参考“图谱”淋巴异质性的新来源的识别和验证查询数据集到多模式图谱的“基于参考”的映射允许使用单个细胞集成多种数据类型的框架被应用于了解不同的免疫细胞状态、以前未识别的免疫群体以及解释对疫苗接种的免疫反应。
The simultaneous measurement of multiple modalities represents an exciting frontier for single-cell genomics and necessitates computational methods that can define cellular states based on multimodal data. Here, we introduce “weighted-nearest neighbor” analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of 211,000 human peripheral blood mononuclear cells (PBMCs) with panels extending to 228 antibodies to construct a multimodal reference atlas of the circulating immune system. Multimodal analysis substantially improves our ability to resolve cell states, allowing us to identify and validate previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets and to interpret immune responses to vaccination and coronavirus disease 2019 (COVID-19). Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets and to look beyond the transcriptome toward a unified and multimodal definition of cellular identity. “Weighted nearest neighbor” analysis integrates multimodal single-cell data A multimodal reference “atlas” of the circulating human immune system Identification and validation of novel sources of lymphoid heterogeneity “Reference-based” mapping of query datasets onto a multimodal atlas A framework that allows for the integration of multiple data types using single cells is applied to understand distinct immune cell states, previously unidentified immune populations, and to interpret immune responses to vaccinations.
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