Abstract
Tissues are constituted of heterogeneous cell types. Although single-cell RNA sequencing has paved the way to a deeper understanding of organismal cellular composition, the high cost and technical noise have prevented its wide application. As an alternative, computational deconvolution of bulk tissues can be a cost-effective solution. In this study, we propose DecOT, a deconvolution method that uses the Wasserstein distance as a loss and applies scRNA-seq data as references to characterize the cell type composition from bulk tissue RNA-seq data. The Wasserstein loss in DecOT is able to utilize additional information from gene space. DecOT also applies an ensemble framework to integrate deconvolution results from multiple individuals' references to mitigate the individual/batch effect. By benchmarking DecOT with four recently proposed square loss-based methods on pseudo-bulk data from four different single-cell data sets and real pancreatic islet bulk samples, we show that DecOT outperforms other methods and the ensemble framework is robust to the choice of references.