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

Nat Commun. 2021 Feb 15;12(1):1029. doi: 10.1038/s41467-021-21312-2.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bayes Theorem
  • Benchmarking
  • Cell Separation / methods
  • Cerebellum / chemistry
  • Cerebellum / cytology
  • Embryo, Mammalian
  • Humans
  • Liver / chemistry
  • Liver / cytology
  • Lung / chemistry
  • Lung / cytology
  • Mice
  • Mouse Embryonic Stem Cells / chemistry
  • Mouse Embryonic Stem Cells / cytology
  • Neural Networks, Computer*
  • Pancreas / chemistry
  • Pancreas / cytology
  • Retina / chemistry
  • Retina / cytology
  • Sequence Analysis, RNA / statistics & numerical data*
  • Single-Cell Analysis / methods
  • Single-Cell Analysis / statistics & numerical data*
  • Unsupervised Machine Learning / statistics & numerical data*
  • Visual Cortex / chemistry
  • Visual Cortex / cytology
  • Zygote / chemistry
  • Zygote / cytology