Fast and Robust Deconvolution of Tumor Infiltrating Lymphocyte from Expression Profiles using Least Trimmed Squares

ABSTRACT Gene-expression deconvolution is used to quantify different types of cells in a mixed population. It provides a highly promising solution to rapidly characterize the tumor-infiltrating immune landscape and identify cold cancers. However, a major challenge is that gene-expression data are frequently contaminated by many outliers that decrease the estimation accuracy. Thus, it is imperative to develop a robust deconvolution method that automatically decontaminates data by reliably detecting and removing outliers. We developed a new machine learning tool, F ast A nd R obust DE convolution of E xpression P rofiles (FARDEEP), to enumerate immune cell subsets from whole tumor tissue samples. To reduce noise in the tumor gene expression datasets, FARDEEP utilizes an adaptive least trimmed square to automatically detect and remove outliers before estimating the cell compositions. We show that FARDEEP is less susceptible to outliers and returns a better estimation of coefficients than the existing methods with both numerical simulations and real datasets. FARDEEP provides the absolute quantitation of each immune cell subset in addition to relative percentages. Hence, FARDEEP represents a novel robust algorithm to complement the existing toolkit for the characterization of tissue-infiltrating immune cell landscape. The source code for FARDEEP as implemented in R is available for download at https://goo.gl/SqGKuo .