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用于单细胞多组学数据联合分析的深度跨组学循环注意力模型。

Deep cross-omics cycle attention model for joint analysis of single-cell multi-omics data.

作者信息

Zuo Chunman, Dai Hao, Chen Luonan

机构信息

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.

Key Laboratory of Systems Health Science of Zhejiang Province, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou 310024, China.

出版信息

Bioinformatics. 2021 Nov 18;37(22):4091-4099. doi: 10.1093/bioinformatics/btab403.

Abstract

MOTIVATION

Joint profiling of single-cell transcriptomics and epigenomics data enables us to characterize cell states and transcriptomics regulatory programs related to cellular heterogeneity. However, the highly different features on sparsity, heterogeneity and dimensionality between multi-omics data have severely hindered its integrative analysis.

RESULTS

We proposed deep cross-omics cycle attention (DCCA) model, a computational tool for joint analysis of single-cell multi-omics data, by combining variational autoencoders (VAEs) and attention-transfer. Specifically, we show that DCCA can leverage one omics data to fine-tune the network trained for another omics data, given a dataset of parallel multi-omics data within the same cell. Studies on both simulated and real datasets from various platforms, DCCA demonstrates its superior capability: (i) dissecting cellular heterogeneity; (ii) denoising and aggregating data and (iii) constructing the link between multi-omics data, which is used to infer new transcriptional regulatory relations. In our applications, DCCA was demonstrated to have a superior power to generate missing stages or omics in a biologically meaningful manner, which provides a new way to analyze and also understand complicated biological processes.

AVAILABILITY AND IMPLEMENTATION

DCCA source code is available at https://github.com/cmzuo11/DCCA, and has been deposited in archived format at https://doi.org/10.5281/zenodo.4762065.

SUPPLEMENTARY INFORMATION

Supplementary data are available at Bioinformatics online.

摘要

动机

单细胞转录组学和表观基因组学数据的联合分析能够让我们表征与细胞异质性相关的细胞状态和转录调控程序。然而,多组学数据在稀疏性、异质性和维度上的巨大差异严重阻碍了其整合分析。

结果

我们提出了深度跨组学循环注意力(DCCA)模型,这是一种用于单细胞多组学数据联合分析的计算工具,它通过结合变分自编码器(VAE)和注意力转移来实现。具体而言,我们表明,给定同一细胞内的平行多组学数据,DCCA能够利用一种组学数据对针对另一种组学数据训练的网络进行微调。在来自各种平台的模拟和真实数据集上的研究表明,DCCA具有卓越的能力:(i)剖析细胞异质性;(ii)对数据进行去噪和聚合;(iii)构建多组学数据之间的联系,用于推断新的转录调控关系。在我们的应用中,DCCA被证明具有以生物学上有意义的方式生成缺失阶段或组学的卓越能力,这为分析和理解复杂的生物过程提供了一种新方法。

可用性和实现方式

DCCA的源代码可在https://github.com/cmzuo11/DCCA获取,并已以存档格式存于https://doi.org/10.5281/zenodo.4762065。

补充信息

补充数据可在《生物信息学》在线获取。

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