Cell composition analysis of bulk genomics using single-cell data

Nat Methods. 2019 Apr;16(4):327-332. doi: 10.1038/s41592-019-0355-5. Epub 2019 Mar 18.

Abstract

Single-cell RNA sequencing (scRNA-seq) is a rich resource of cellular heterogeneity, opening new avenues in the study of complex tissues. We introduce Cell Population Mapping (CPM), a deconvolution algorithm in which reference scRNA-seq profiles are leveraged to infer the composition of cell types and states from bulk transcriptome data ('scBio' CRAN R-package). Analysis of individual variations in lungs of influenza-virus-infected mice reveals that the relationship between cell abundance and clinical symptoms is a cell-state-specific property that varies gradually along the continuum of cell-activation states. The gradual change is confirmed in subsequent experiments and is further explained by a mathematical model in which clinical outcomes relate to cell-state dynamics along the activation process. Our results demonstrate the power of CPM in reconstructing the continuous spectrum of cell states within heterogeneous tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Cell Separation
  • Computational Biology*
  • Female
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Gene Expression Profiling
  • Genome, Human
  • Genomics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lung / virology
  • Markov Chains
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae
  • Phagocytes / metabolism
  • Reference Values
  • Sequence Analysis, RNA*
  • Single-Cell Analysis*
  • Software
  • Transcriptome