4.8 Article

Fast and precise single-cell data analysis using a hierarchical autoencoder

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41467-021-21312-2

Keywords

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Funding

  1. NASA [80NSSC19M0170, NNX15AI02H, 21-02]
  2. NIH NIGMS [GM103440]
  3. NSF [2001385, 2019609]

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Accurate analysis of single-cell RNA sequencing (scRNA-seq) data is crucial for various research fields, but is often hindered by technical noise and high dropout rates. The hierarchical autoencoder, scDHA, introduced in this study, outperforms existing methods in various aspects of scRNA-seq analysis, including cell segregation and classification.
A primary challenge in single-cell RNA sequencing (scRNA-seq) studies comes from the massive amount of data and the excess noise level. To address this challenge, we introduce an analysis framework, named single-cell Decomposition using Hierarchical Autoencoder (scDHA), that reliably extracts representative information of each cell. The scDHA pipeline consists of two core modules. The first module is a non-negative kernel autoencoder able to remove genes or components that have insignificant contributions to the part-based representation of the data. The second module is a stacked Bayesian autoencoder that projects the data onto a low-dimensional space (compressed). To diminish the tendency to overfit of neural networks, we repeatedly perturb the compressed space to learn a more generalized representation of the data. In an extensive analysis, we demonstrate that scDHA outperforms state-of-the-art techniques in many research sub-fields of scRNA-seq analysis, including cell segregation through unsupervised learning, visualization of transcriptome landscape, cell classification, and pseudo-time inference. Accurate analysis of single-cell RNA sequencing (scRNA-seq) data is affected by issues including technical noise and high dropout rate. Here, the authors develop a hierarchical autoencoder, scDHA, which outperforms existing methods in scRNA-seq analyses such as cell segregation and classification.

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