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基于自动编码器的单细胞 RNA 测序数据分析。

Analysis of single-cell RNA sequencing data based on autoencoders.

机构信息

Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Cambridge, CB2 0AW, UK.

Department of Haematology, University of Cambridge, Cambridge, CB2 0AW, UK.

出版信息

BMC Bioinformatics. 2021 Jun 8;22(1):309. doi: 10.1186/s12859-021-04150-3.

Abstract

BACKGROUND

Single-cell RNA sequencing (scRNA-Seq) experiments are gaining ground to study the molecular processes that drive normal development as well as the onset of different pathologies. Finding an effective and efficient low-dimensional representation of the data is one of the most important steps in the downstream analysis of scRNA-Seq data, as it could provide a better identification of known or putatively novel cell-types. Another step that still poses a challenge is the integration of different scRNA-Seq datasets. Though standard computational pipelines to gain knowledge from scRNA-Seq data exist, a further improvement could be achieved by means of machine learning approaches.

RESULTS

Autoencoders (AEs) have been effectively used to capture the non-linearities among gene interactions of scRNA-Seq data, so that the deployment of AE-based tools might represent the way forward in this context. We introduce here scAEspy, a unifying tool that embodies: (1) four of the most advanced AEs, (2) two novel AEs that we developed on purpose, (3) different loss functions. We show that scAEspy can be coupled with various batch-effect removal tools to integrate data by different scRNA-Seq platforms, in order to better identify the cell-types. We benchmarked scAEspy against the most used batch-effect removal tools, showing that our AE-based strategies outperform the existing solutions.

CONCLUSIONS

scAEspy is a user-friendly tool that enables using the most recent and promising AEs to analyse scRNA-Seq data by only setting up two user-defined parameters. Thanks to its modularity, scAEspy can be easily extended to accommodate new AEs to further improve the downstream analysis of scRNA-Seq data. Considering the relevant results we achieved, scAEspy can be considered as a starting point to build a more comprehensive toolkit designed to integrate multi single-cell omics.

摘要

背景

单细胞 RNA 测序(scRNA-Seq)实验正在兴起,用于研究驱动正常发育以及不同病理发生的分子过程。在 scRNA-Seq 数据的下游分析中,找到数据的有效且高效的低维表示是最重要的步骤之一,因为它可以更好地识别已知或推测的新型细胞类型。另一个仍然具有挑战性的步骤是整合不同的 scRNA-Seq 数据集。尽管存在用于从 scRNA-Seq 数据中获取知识的标准计算流程,但通过机器学习方法可以进一步改进。

结果

自动编码器(AEs)已被有效地用于捕获 scRNA-Seq 数据中基因相互作用的非线性,因此基于 AE 的工具的部署可能代表了这方面的前进方向。我们在这里介绍 scAEspy,这是一个统一的工具,它包含:(1)四种最先进的 AE,(2)我们专门开发的两种新型 AE,(3)不同的损失函数。我们表明,scAEspy 可以与各种批次效应去除工具结合使用,以通过不同的 scRNA-Seq 平台整合数据,从而更好地识别细胞类型。我们将 scAEspy 与最常用的批次效应去除工具进行了基准测试,结果表明我们基于 AE 的策略优于现有解决方案。

结论

scAEspy 是一个用户友好的工具,只需设置两个用户定义的参数即可使用最新且最有前途的 AE 来分析 scRNA-Seq 数据。由于其模块化,scAEspy 可以轻松扩展以适应新的 AE,从而进一步改进 scRNA-Seq 数据的下游分析。考虑到我们取得的相关结果,scAEspy 可以被视为构建更全面的工具箱的起点,该工具箱旨在整合多单细胞组学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dd9/8186186/c3c0ec46b62f/12859_2021_4150_Fig1_HTML.jpg

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