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Infino: a Bayesian hierarchical model improves estimates of immune infiltration into tumor microenvironment

View ORCID ProfileMaxim Zaslavsky, View ORCID ProfileJacqueline Buros Novik, View ORCID ProfileEliza Chang, View ORCID ProfileJeffrey Hammerbacher
doi: https://doi.org/10.1101/221671
Maxim Zaslavsky
1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029
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Jacqueline Buros Novik
1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029
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Eliza Chang
1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029
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Jeffrey Hammerbacher
1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029
2Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425
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Abstract

Robust quantification of immune cell infiltration into the tumor microenvironment may shed light on why only a small proportion of patients benefit from checkpoint therapy. The immune cells surrounding a tumor have been suggested to mediate an effective response to immunotherapy. However, traditional measurement of immune cell content around a tumor by immunohistochemistry, flow cytometry, or mass cytometry allows measurement of only up to a few dozen markers at a time, limiting the number of immune cell types identified. Immune cell type abundances may instead be estimated in silico by deconvolving gene expression mixtures from bulk RNA sequencing of tumor tissue. By measuring tens of thousands of transcripts at once, bulk RNA-seq provides a rich input to algorithms that quantify cell type abundances in the tumor microenvironment, affording the potential to quantify the states of a greater number of immune cell types (given adequate training data). Here, we first review existing methods for deconvolution and evaluate their performance on synthetic mixtures. Then we develop a Bayesian inference approach, named infino, that learns to distinguish immune cell expression phenotypes and deconvolve mixtures. In contrast to earlier approaches, infino accepts RNA sequencing data, models transcript expression variability, and exploits the relationships between cell types to improve deconvolution accuracy and allow interrogation from the level of broad categories to the level of finest granularity. The resulting probability distributions of immune infiltration could be applied to numerous questions concerning the diverse ecology of immune cell types, including assessment of the association of immune infiltration with response to immunotherapy, and study of the expression profile and presence of elusive T cell subcompartments, such as T cell exhaustion.

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Posted November 21, 2017.
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Infino: a Bayesian hierarchical model improves estimates of immune infiltration into tumor microenvironment
Maxim Zaslavsky, Jacqueline Buros Novik, Eliza Chang, Jeffrey Hammerbacher
bioRxiv 221671; doi: https://doi.org/10.1101/221671
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Infino: a Bayesian hierarchical model improves estimates of immune infiltration into tumor microenvironment
Maxim Zaslavsky, Jacqueline Buros Novik, Eliza Chang, Jeffrey Hammerbacher
bioRxiv 221671; doi: https://doi.org/10.1101/221671

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