Fast and robust deconvolution of tumor infiltrating lymphocyte from expression profiles using least trimmed squares

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, Fast And Robust DEconvolution of Expression Profiles (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 an estimate related to the absolute quantity 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 is implemented in R and available for download at https://github.com/YuningHao/FARDEEP.git. Author summary Rapidly emerging evidence suggests that the tumor immune microenvironment not only predisposes cancer patients to diverse treatment outcomes but also represents a promising source of biomarkers for better patient stratification. Different from the immunohistochemistry-based scoring practice, which focuses on a few selected marker proteins, immune deconvolution pipelines inform a previously untapped method to comprehensively reveal the tumor-infiltrating immune landscape. Recognizing the numerous strengths of existing immune deconvolution algorithms, here we show data outliers, which are inevitable in whole tissue sequencing data sets, substantially skew estimation results. Moreover, an estimate related to the absolute amount of each immune subset offers valuable insight into the nature of the host response in addition to percentage information alone. Thus, we engineered a new immune deconvolution pipeline, coined as Fast and Robust Deconvolution of Expression Profiles (FARDEEP), to automatically detect and remove outliers prior feeding data into the deconvolution algorithm and to provide estimates related to the absolute quantity of each immune subset. Utilizing both synthetic and real data sets, we found that FARDEEP returns superior coefficients and offers a robust tool to reveal the immune landscape of human cancers.