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Comprehensive evaluation of computational cell-type quantification methods for immuno-oncology

By Gregor Sturm, Francesca Finotello, Florent Petitprez, David Jitao Zhang, Jan Baumbach, Wolf H Fridman, Markus List, Tatsiana Aneichyk

Posted 06 Nov 2018
bioRxiv DOI: 10.1101/463828 (published DOI: 10.1093/bioinformatics/btz363)

Motivation: The composition and density of immune cells in the tumor microenvironment profoundly influence tumor progression and success of anti-cancer therapies. Flow cytometry, immunohistochemistry staining, or single-cell sequencing is often unavailable such that we rely on computational methods to estimate the immune-cell composition from bulk RNA-sequencing (RNA-seq) data. Various methods have been proposed recently, yet their capabilities and limitations have not been evaluated systematically. A general guideline leading the research community through cell type deconvolution is missing. Results: We developed a systematic approach for benchmarking such computational methods and assessed the accuracy of tools at estimating nine different immune- and stromal cells from bulk RNA-seq samples. We used a single-cell RNA-seq dataset of ~11,000 cells from the tumor microenvironment to simulate bulk samples of known cell type proportions, and validated the results using independent, publicly available gold-standard estimates. This allowed us to analyze and condense the results of more than a hundred thousand predictions to provide an exhaustive evaluation across seven computational methods over nine cell types and ~1,800 samples from five simulated and real-world datasets. We demonstrate that computational deconvolution performs at high accuracy for well-defined cell-type signatures and propose how fuzzy cell-type signatures can be improved. We suggest that future efforts should be dedicated to refining cell population definitions and finding reliable signatures. Availability: A snakemake pipeline to reproduce the benchmark is available at https://github.com/grst/immune_deconvolution_benchmark. An R package allows the community to perform integrated deconvolution using different methods (https://grst.github.io/immunedeconv).

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