ICeD-T Provides Accurate Estimates of Immune Cell Abundance in Tumor Samples by Allowing for Aberrant Gene Expression Patterns

Immunotherapies have attracted lots of research interests recently. The need to understand the underlying mechanisms of immunotherapies and to develop precision immunotherapy regimens has spurred great interest in characterizing immune cell composition within the tumor microenvironment. Several methods have been developed to estimate immune cell composition using gene expression data from bulk tumor samples. However, these methods are not flexible enough to handle aberrant patterns of gene expression data, for example, inconsistent cell type-specific gene expression between purified reference samples and tumor samples. We propose a novel statistical method for expression deconvolution called immune cell deconvolution in tumor tissues (ICeD-T). ICeD-T automatically identifies aberrant genes whose expression are inconsistent with the deconvolution model and down-weights their contributions to cell type abundance estimates. We evaluated the performance of ICeD-T versus existing methods in simulation studies and several real data analyses. ICeD-T displayed comparable or superior performance to these competing methods. Applying these methods to assess the relationship between immunotherapy response and immune cell composition, ICeD-T is able to identify significant associations that are missed by its competitors. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.