Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data

Elife. 2017 Nov 13:6:e26476. doi: 10.7554/eLife.26476.

Abstract

Immune cells infiltrating tumors can have important impact on tumor progression and response to therapy. We present an efficient algorithm to simultaneously estimate the fraction of cancer and immune cell types from bulk tumor gene expression data. Our method integrates novel gene expression profiles from each major non-malignant cell type found in tumors, renormalization based on cell-type-specific mRNA content, and the ability to consider uncharacterized and possibly highly variable cell types. Feasibility is demonstrated by validation with flow cytometry, immunohistochemistry and single-cell RNA-Seq analyses of human melanoma and colorectal tumor specimens. Altogether, our work not only improves accuracy but also broadens the scope of absolute cell fraction predictions from tumor gene expression data, and provides a unique novel experimental benchmark for immunogenomics analyses in cancer research (http://epic.gfellerlab.org).

Keywords: cancer biology; cell fraction predictions; computational biology; gene expression; human; systems biology; tumor immune microenvironment.

Publication types

  • Validation Study

MeSH terms

  • Cell Count / methods*
  • Colorectal Neoplasms / pathology*
  • Flow Cytometry
  • Gene Expression Profiling / methods*
  • Humans
  • Immunohistochemistry
  • Melanoma / pathology*
  • Pathology, Molecular / methods*
  • Sequence Analysis, RNA

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.