Estimation of immune cell content in tumor using single-cell RNA-seq reference data

BMC Cancer. 2019 Jul 19;19(1):715. doi: 10.1186/s12885-019-5927-3.

Abstract

Background: The rapid development of single-cell RNA sequencing (scRNA-seq) provides unprecedented opportunities to study the tumor ecosystem that involves a heterogeneous mixture of cell types. However, the majority of previous and current studies related to translational and molecular oncology have only focused on the bulk tumor and there is a wealth of gene expression data accumulated with matched clinical outcomes.

Results: In this paper, we introduce a scheme for characterizing cell compositions from bulk tumor gene expression by integrating signatures learned from scRNA-seq data. We derived the reference expression matrix to each cell type based on cell subpopulations identified in head and neck cancer dataset. Our results suggest that scRNA-Seq-derived reference matrix outperforms the existing gene panel and reference matrix with respect to distinguishing immune cell subtypes.

Conclusions: Findings and resources created from this study enable future and secondary analysis of tumor RNA mixtures in head and neck cancer for a more accurate cellular deconvolution, and can facilitate the profiling of the immune infiltration in other solid tumors due to the expression homogeneity observed in immune cells.

Keywords: Head and neck cancer; Reference gene expression profiles; Single-cell RNA-seq; Tumor-infiltrating lymphocyte.

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • Databases, Genetic
  • Datasets as Topic
  • Ecosystem
  • Genes, Neoplasm
  • Genetic Heterogeneity
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / immunology*
  • Head and Neck Neoplasms / pathology
  • Humans
  • RNA, Small Cytoplasmic / genetics
  • RNA-Seq / methods*
  • Single-Cell Analysis / methods*
  • Software
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / immunology*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • Transcriptome
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • RNA, Small Cytoplasmic