Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 65,445 bioRxiv papers from 289,895 authors.
Recent advances in single-cell RNA sequencing (scRNA-seq) enable characterization of transcriptomic profiles with single-cell resolution and circumvent averaging artifacts associated with traditional bulk RNA sequencing (RNA-seq) data. Here, we propose SCDC, a deconvolution method for bulk RNA-seq that leverages cell-type specific gene expression profiles from multiple scRNA-seq reference datasets. SCDC adopts an ENSEMBLE method to integrate deconvolution results from different scRNA-seq datasets that are produced in different laboratories and at different times, implicitly addressing the problem of batch-effect confounding. SCDC is benchmarked against existing methods using both in silico generated pseudo-bulk samples and experimentally mixed cell lines, whose known cell-type compositions serve as ground truths. We show that SCDC outperforms existing methods with improved accuracy of cell-type decomposition under both settings. To illustrate how the ENSEMBLE framework performs in complex tissues under different scenarios, we further apply our method to a human pancreatic islet dataset and a mouse mammary gland dataset. SCDC returns results that are more consistent with experimental designs and that reproduce more significant associations between cell-type proportions and measured phenotypes.
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