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

56 Pages Posted: 26 Feb 2019 Sneak Peek Status: Published

See all articles by Gianni Monaco

Gianni Monaco

University of Basel - Department of Biomedicine

Bernett Lee

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Weili Xu

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Seri Mustafah

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

You Yi Hwang

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Christophe Carré

Sanofi Pasteur

Nicolas Burdin

Sanofi Pasteur

Lucian Visan

Sanofi Pasteur

Alfred Zippelius

University of Basel - Department of Biomedicine

Michele Ceccarelli

BIOGEM Research Center

Michael Poidinger

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

João Pedro de Magalhães

University of Liverpool - Institute of Ageing and Chronic Disease

Anis Larbi

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

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Abstract

The molecular characterization of immune cell types is important for designing and developing effective strategies to understand and treat diseases. We characterized 29 different immune cell types within the peripheral blood mononuclear cell (PBMC) fraction of healthy donors using RNA sequencing (RNA-Seq) and flow cytometry. Our RNA-Seq resource has been used first to identify set of genes that are specific, co-expressed and have housekeeping role across the 29 immune cell types. Then, we analyzed the RNA composition for each immune cell type in terms of their relative mRNA heterogeneity and abundance. Lastly, we develop a novel method of gene expression normalization in order to perform absolute deconvolution at a fine resolution from both RNA-Seq and microarray datasets. The resources were validated in independent cohorts and benchmarked with different deconvolution and normalization methods. We believe that this work has clinical and diagnostic value by allowing us to attribute observations in bulk RNA data to specific immune cell populations.

Suggested Citation

Monaco, Gianni and Lee, Bernett and Xu, Weili and Mustafah, Seri and Hwang, You Yi and Carré, Christophe and Burdin, Nicolas and Visan, Lucian and Zippelius, Alfred and Ceccarelli, Michele and Poidinger, Michael and Magalhães, João Pedro de and Larbi, Anis, RNA-Seq Signatures Normalized by mRNA Abundance Allow Absolute Deconvolution of Human Immune Cells (September 14, 2018). Available at SSRN: https://ssrn.com/abstract=3249819 or http://dx.doi.org/10.2139/ssrn.3249819
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Gianni Monaco (Contact Author)

University of Basel - Department of Biomedicine ( email )

Petersplatz 1
Basel, CH-4003
Switzerland

Bernett Lee

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN) ( email )

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Weili Xu

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Seri Mustafah

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

You Yi Hwang

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Christophe Carré

Sanofi Pasteur

2 av. Pont Pasteur
Lyon cedex 07, 69367
France

Nicolas Burdin

Sanofi Pasteur

2 av. Pont Pasteur
Lyon cedex 07, 69367
France

Lucian Visan

Sanofi Pasteur

2 av. Pont Pasteur
Lyon cedex 07, 69367
France

Alfred Zippelius

University of Basel - Department of Biomedicine

Petersplatz 1
Basel, CH-4003
Switzerland

Michele Ceccarelli

BIOGEM Research Center

Ariano Irpino
Italy

Michael Poidinger

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

João Pedro de Magalhães

University of Liverpool - Institute of Ageing and Chronic Disease

Brownlow Hill
Liverpool, L69 3BX
United Kingdom

Anis Larbi

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

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