Abstract
Differential expression using RNA sequencing data 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. Differential expression analysis without accounting for cell type composition cannot separate the changes due to cell type composition or cell type-specific expression. In addition, cell type-specific signals may be masked or even misrepresented, especially for relatively rare cell types. We propose a new framework to address these limitations: Cell Type Aware analysis of RNA-seq (CARseq). After evaluating its performance in simulations, we apply CARseq to compare gene expression of schizophrenia/autism subjects versus controls. Our results show that these two neurodevelopmental disorders differ from each other in terms of cell type composition changes and genes related with different types of neurotransmitter receptors were differentially expressed in neuron cells. We also discover some overlapping signals of differential expression in microglia, supporting the two diseases’ similarity through immune regulation.
Competing Interest Statement
The authors have declared no competing interest.