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

Abstract
Data availability
Article and author information
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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

(2017) Simultaneous enumeration of cancer and immune cell types from tumor gene expression data
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE93722).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE93722

The following previously published data sets were used

1. Poland G
(2015) Bioinformatics Approach to 2010-2011 TIV Influenza A/H1N1 Vaccine Immune Profiling
Available at ImmPort (accession no: SDY67).

http://www.immport.org/immport-open/public/study/study/displayStudyDetail/SDY67
1. Hoek KL
2. Link AJ
(2015) A Cell-based Systems Biology Assessment of Human Blood to Monitor Immune Responses After Influenza Vaccination
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE64655).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE64655
1. Speake C
2. Linsley PS
3. Whalen E
4. Chaussabel D
5. Presnell SR
6. Mason MJ
7. Gersuk VH
8. O'Brien KK
9. Nguyen Q
10. Greenbaum CJ
11. Buckner JH
12. Malhotra U
(2015) Next generation sequencing of human immune cell subsets across diseases
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE60424).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60424
(2016) RNA-Seq analysis of human adult peripheral blood populations
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE51984).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51984
1. Marisa L
2. de Reyniès A
3. Duval A
4. Selves J
5. Gaub M
6. Vescovo L
7. Etienne-Grimaldi M
8. Schiappa R
9. Guenot D
10. Ayadi M
11. Kirzin S
12. Chazal M
13. Fléjou J
14. Benchimol D
15. Pencreach E
16. Lagarde A
17. Piard F
18. Elias D
19. Olschwang S
20. Milano G
21. Laurent-Puig P
22. Boige V
(2013) Gene expression Classification of Colon Cancer defines six molecular subtypes with distinct clinical, molecular and survival characteristics [Expression]
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE39582).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39582
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).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72056

Article and author information

Author details

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.

"This ORCID iD identifies the author of this article:" 0000-0002-0100-0323
Kaat de Jonge

Department of Fundamental Oncology, Lausanne University Hospital, Epalinges, Switzerland

Competing interests
The authors declare that no competing interests exist.
Petra Baumgaertner

Department of Fundamental Oncology, Lausanne University Hospital, Epalinges, Switzerland

Competing interests
The authors declare that no competing interests exist.
Daniel E Speiser

Department of Fundamental Oncology, Lausanne University Hospital, Epalinges, Switzerland

Competing interests
The authors declare that no competing interests exist.
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.

"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.

Copyright

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.