RNA-Seq Signatures Normalized by mRNA Abundance Allow Absolute Deconvolution of Human Immune Cell Types

Gianni Monaco, Bernett Lee, Weili Xu, Seri Mustafah, You Yi Hwang, Christophe Carré, Nicolas Burdin, Lucian Visan, Michele Ceccarelli, Michael Poidinger, Alfred Zippelius, João Pedro de Magalhães, Anis Larbi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The molecular characterization of immune subsets is important for designing effective strategies to understand and treat diseases. We characterized 29 immune cell types within the peripheral blood mononuclear cell (PBMC) fraction of healthy donors using RNA-seq (RNA sequencing) and flow cytometry. Our dataset was used, first, to identify sets of genes that are specific, are co-expressed, and have housekeeping roles across the 29 cell types. Then, we examined differences in mRNA heterogeneity and mRNA abundance revealing cell type specificity. Last, we performed absolute deconvolution on a suitable set of immune cell types using transcriptomics signatures normalized by mRNA abundance. Absolute deconvolution is ready to use for PBMC transcriptomic data using our Shiny app (https://github.com/giannimonaco/ABIS). We benchmarked different deconvolution and normalization methods and validated the resources in independent cohorts. Our work has research, clinical, and diagnostic value by making it possible to effectively associate observations in bulk transcriptomics data to specific immune subsets.

Original languageEnglish
Pages (from-to)1627-1640.e7
JournalCell Reports
Volume26
Issue number6
DOIs
Publication statusPublished - 5 Feb 2019
Externally publishedYes

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Keywords

  • deconvolution
  • flow cytometry
  • gene modules
  • housekeeping
  • immune system
  • mRNA abundance
  • mRNA composition
  • mRNA heterogeneity
  • RNA-seq
  • transcriptome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Monaco, G., Lee, B., Xu, W., Mustafah, S., Hwang, Y. Y., Carré, C., Burdin, N., Visan, L., Ceccarelli, M., Poidinger, M., Zippelius, A., Pedro de Magalhães, J., & Larbi, A. (2019). RNA-Seq Signatures Normalized by mRNA Abundance Allow Absolute Deconvolution of Human Immune Cell Types. Cell Reports, 26(6), 1627-1640.e7. https://doi.org/10.1016/j.celrep.2019.01.041