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基于生成对抗网络的单细胞转录组深度特征提取。

Deep feature extraction of single-cell transcriptomes by generative adversarial network.

机构信息

School of Computer Science, McGill Centre for Bioinformatics, McGill University, Montreal, QC H3A 0E9, Canada.

Department of Computer Engineering, Sharif University of Technology, Tehran 11365-11155, Iran.

出版信息

Bioinformatics. 2021 Jun 16;37(10):1345-1351. doi: 10.1093/bioinformatics/btaa976.

Abstract

MOTIVATION

Single-cell RNA-sequencing (scRNA-seq) offers the opportunity to dissect heterogeneous cellular compositions and interrogate the cell-type-specific gene expression patterns across diverse conditions. However, batch effects such as laboratory conditions and individual-variability hinder their usage in cross-condition designs.

RESULTS

Here, we present a single-cell Generative Adversarial Network (scGAN) to simultaneously acquire patterns from raw data while minimizing the confounding effect driven by technical artifacts or other factors inherent to the data. Specifically, scGAN models the data likelihood of the raw scRNA-seq counts by projecting each cell onto a latent embedding. Meanwhile, scGAN attempts to minimize the correlation between the latent embeddings and the batch labels across all cells. We demonstrate scGAN on three public scRNA-seq datasets and show that our method confers superior performance over the state-of-the-art methods in forming clusters of known cell types and identifying known psychiatric genes that are associated with major depressive disorder.

AVAILABILITYAND IMPLEMENTATION

The scGAN code and the information for the public scRNA-seq datasets are available at https://github.com/li-lab-mcgill/singlecell-deepfeature.

SUPPLEMENTARY INFORMATION

Supplementary data are available at Bioinformatics online.

摘要

动机

单细胞 RNA 测序(scRNA-seq)提供了一种机会,可以剖析异质细胞组成,并在不同条件下研究细胞类型特异性基因表达模式。然而,批次效应(如实验室条件和个体差异)会影响其在跨条件设计中的应用。

结果

在这里,我们提出了一种单细胞生成对抗网络(scGAN),同时从原始数据中获取模式,同时最小化由技术伪影或数据中固有其他因素引起的混杂效应。具体来说,scGAN 通过将每个细胞投影到潜在嵌入上来对原始 scRNA-seq 计数的似然性建模。同时,scGAN 试图最小化所有细胞中潜在嵌入和批次标签之间的相关性。我们在三个公开的 scRNA-seq 数据集上展示了 scGAN,并表明我们的方法在形成已知细胞类型的聚类和识别与重度抑郁症相关的已知精神疾病基因方面优于最先进的方法。

可用性和实现

scGAN 代码和公共 scRNA-seq 数据集的信息可在 https://github.com/li-lab-mcgill/singlecell-deepfeature 上获得。

补充信息

补充数据可在《生物信息学》在线获得。

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