SCDC: bulk gene expression deconvolution by multiple single-cell RNA sequencing references

Brief Bioinform. 2021 Jan 18;22(1):416-427. doi: 10.1093/bib/bbz166.


Recent advances in single-cell RNA sequencing (scRNA-seq) enable characterization of transcriptomic profiles with single-cell resolution and circumvent averaging artifacts associated with traditional bulk RNA sequencing (RNA-seq) data. Here, we propose SCDC, a deconvolution method for bulk RNA-seq that leverages cell-type specific gene expression profiles from multiple scRNA-seq reference datasets. SCDC adopts an ENSEMBLE method to integrate deconvolution results from different scRNA-seq datasets that are produced in different laboratories and at different times, implicitly addressing the problem of batch-effect confounding. SCDC is benchmarked against existing methods using both in silico generated pseudo-bulk samples and experimentally mixed cell lines, whose known cell-type compositions serve as ground truths. We show that SCDC outperforms existing methods with improved accuracy of cell-type decomposition under both settings. To illustrate how the ENSEMBLE framework performs in complex tissues under different scenarios, we further apply our method to a human pancreatic islet dataset and a mouse mammary gland dataset. SCDC returns results that are more consistent with experimental designs and that reproduce more significant associations between cell-type proportions and measured phenotypes.

Keywords: ENSEMBLE; batch effect; bulk RNA sequencing; gene expression deconvolution; single-cell RNA sequencing.

Publication types

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

MeSH terms

  • Animals
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Islets of Langerhans / metabolism
  • MCF-7 Cells
  • Mammary Glands, Animal / metabolism
  • Mice
  • RNA-Seq / methods*
  • RNA-Seq / standards
  • Reference Standards
  • Single-Cell Analysis / methods*
  • Single-Cell Analysis / standards
  • Software / standards*