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Cell Rep. 2019 Feb 5;26(6):1627-1640.e7. doi: 10.1016/j.celrep.2019.01.041.

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

Author information

1
Singapore Immunology Network (SIgN), Agency for Science Technology and Research, Biopolis, 8A Biomedical Grove, 138648, Singapore, Singapore; Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L78TX, UK; Department of Biomedicine, University Hospital and University of Basel, 4031 Basel, Switzerland. Electronic address: mongianni1@gmail.com.
2
Singapore Immunology Network (SIgN), Agency for Science Technology and Research, Biopolis, 8A Biomedical Grove, 138648, Singapore, Singapore.
3
Sanofi Pasteur, Marcy l'Etoile, France.
4
BIOGEM Research Center, Ariano Irpino, Italy; Department of Science and Technology, University of Sannio, Benevento, Italy.
5
Department of Biomedicine, University Hospital and University of Basel, 4031 Basel, Switzerland.
6
Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L78TX, UK. Electronic address: jp@senescence.info.
7
Singapore Immunology Network (SIgN), Agency for Science Technology and Research, Biopolis, 8A Biomedical Grove, 138648, Singapore, Singapore; Department of Biology, Faculty of Sciences, University Tunis El Manar, Tunis, Tunisia; Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC, Canada; Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address: anis_larbi@immunol.a-star.edu.sg.

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.

KEYWORDS:

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

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