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Abstract:
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Differential expression using RNA sequencing of bulk tissue samples (bulk RNA-seq) is a very popular and effective approach to study many biomedical problems. However, most tissue samples are composed of different cell types, presenting challenges to the analysis of bulk RNA-seq, which aggregates gene expression across multiple types of cells. Methods without accounting for cell type composition may mask or even misrepresent important cell type-specific signals, especially for relatively rare cell types. In addition, differential expression using bulk RNA-seq cannot distinguish the effects of differential cell type composition or differential expression of individual cell types. We propose a method to address these limitations: cell type-aware differential expression analysis. Our method tests cell type-specific differential expression using bulk RNA-seq data by incorporating the information of cell type composition, which can be estimated separately using an existing method. We demonstrate the performance of our method in both simulations and real data analysis.
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