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

  1. Julien Racle
  2. Kaat de Jonge
  3. Petra Baumgaertner
  4. Daniel E Speiser
  5. David Gfeller  Is a corresponding author
  1. University of Lausanne, Switzerland
  2. Lausanne University Hospital, Switzerland

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.

Data availability

The following data sets were generated
The following previously published data sets were used
    1. Tirosh I
    2. Izar B
    (2016) Single cell RNA-seq analysis of melanoma
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE72056).

Article and author information

Author details

  1. Julien Racle

    Ludwig Centre for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0100-0323
  2. Kaat de Jonge

    Department of Fundamental Oncology, Lausanne University Hospital, Epalinges, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Petra Baumgaertner

    Department of Fundamental Oncology, Lausanne University Hospital, Epalinges, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel E Speiser

    Department of Fundamental Oncology, Lausanne University Hospital, Epalinges, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. David Gfeller

    Ludwig Centre for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
    For correspondence
    david.gfeller@unil.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3952-0930

Funding

Center for Advanced Modelling Science

  • Julien Racle
  • David Gfeller

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Project grant 31003A_173156)

  • Julien Racle
  • David Gfeller

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

Ethics

Human subjects: Patients involved in this study agreed to donate metastatic tissues upon informed consent, based on dedicated clinical investigation protocols established according to the relevant regulatory standards. The protocols were approved by the local IRB, i.e. the Commission cantonale d'éthique de la recherche sur l'être humain du Canton de Vaud.

Reviewing Editor

  1. Alfonso Valencia, Barcelona Supercomputing Center - BSC, Spain

Publication history

  1. Received: March 2, 2017
  2. Accepted: November 10, 2017
  3. Accepted Manuscript published: November 13, 2017 (version 1)
  4. Version of Record published: December 6, 2017 (version 2)

Copyright

© 2017, Racle et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Julien Racle
  2. Kaat de Jonge
  3. Petra Baumgaertner
  4. Daniel E Speiser
  5. David Gfeller
(2017)
Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data
eLife 6:e26476.
https://doi.org/10.7554/eLife.26476

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