Model-based deep embedding for constrained clustering analysis of single cell RNA-seq data

Tian Tian, Jie Zhang, Xiang Lin, Zhi Wei, Hakon Hakonarson

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Clustering is a critical step in single cell-based studies. Most existing methods support unsupervised clustering without the a priori exploitation of any domain knowledge. When confronted by the high dimensionality and pervasive dropout events of scRNA-Seq data, purely unsupervised clustering methods may not produce biologically interpretable clusters, which complicates cell type assignment. In such cases, the only recourse is for the user to manually and repeatedly tweak clustering parameters until acceptable clusters are found. Consequently, the path to obtaining biologically meaningful clusters can be ad hoc and laborious. Here we report a principled clustering method named scDCC, that integrates domain knowledge into the clustering step. Experiments on various scRNA-seq datasets from thousands to tens of thousands of cells show that scDCC can significantly improve clustering performance, facilitating the interpretability of clusters and downstream analyses, such as cell type assignment.

Original languageEnglish (US)
Article number1873
JournalNature communications
Issue number1
StatePublished - Dec 1 2021

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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