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用于单细胞RNA测序数据功能注释的单细胞基因集富集分析和迁移学习

Single-cell gene set enrichment analysis and transfer learning for functional annotation of scRNA-seq data.

作者信息

Franchini Melania, Pellecchia Simona, Viscido Gaetano, Gambardella Gennaro

机构信息

Telethon Institute of Genetics and Medicine, Pozzuoli 80078 Naples, Italy.

Department of Electrical Engineering and Information Technologies, University of Naples Federico II, 80125 Naples, Italy.

出版信息

NAR Genom Bioinform. 2023 Mar 3;5(1):lqad024. doi: 10.1093/nargab/lqad024. eCollection 2023 Mar.

Abstract

Although an essential step, cell functional annotation often proves particularly challenging from single-cell transcriptional data. Several methods have been developed to accomplish this task. However, in most cases, these rely on techniques initially developed for bulk RNA sequencing or simply make use of marker genes identified from cell clustering followed by supervised annotation. To overcome these limitations and automatize the process, we have developed two novel methods, the single-cell gene set enrichment analysis (scGSEA) and the single-cell mapper (scMAP). scGSEA combines latent data representations and gene set enrichment scores to detect coordinated gene activity at single-cell resolution. scMAP uses transfer learning techniques to re-purpose and contextualize new cells into a reference cell atlas. Using both simulated and real datasets, we show that scGSEA effectively recapitulates recurrent patterns of pathways' activity shared by cells from different experimental conditions. At the same time, we show that scMAP can reliably map and contextualize new single-cell profiles on a breast cancer atlas we recently released. Both tools are provided in an effective and straightforward workflow providing a framework to determine cell function and significantly improve annotation and interpretation of scRNA-seq data.

摘要

尽管细胞功能注释是一个必不可少的步骤,但从单细胞转录数据来看,它往往极具挑战性。已经开发了几种方法来完成这项任务。然而,在大多数情况下,这些方法依赖于最初为批量RNA测序开发的技术,或者只是简单地利用从细胞聚类中识别出的标记基因,然后进行监督注释。为了克服这些限制并使过程自动化,我们开发了两种新方法,即单细胞基因集富集分析(scGSEA)和单细胞映射器(scMAP)。scGSEA结合潜在数据表示和基因集富集分数,以单细胞分辨率检测协调的基因活性。scMAP使用迁移学习技术将新细胞重新用于参考细胞图谱并进行背景分析。使用模拟数据集和真实数据集,我们表明scGSEA有效地概括了来自不同实验条件的细胞共有的通路活性的复发模式。同时,我们表明scMAP可以在我们最近发布的乳腺癌图谱上可靠地映射和背景化新的单细胞图谱。这两种工具都以有效且直接的工作流程提供,为确定细胞功能以及显著改善scRNA-seq数据的注释和解释提供了一个框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d5/9985338/ef842ed5718d/lqad024fig1.jpg

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