Cell composition analysis of bulk genomics using single cell data

Single-cell expression profiling is a rich resource of cellular heterogeneity. While profiling every sample under study is advantageous, such workflow is time consuming and costly. We devised CPM - a deconvolution algorithm in which cellular heterogeneity is inferred from bulk expression data based on pre-existing collection of single-cell RNA-seq profiles. We applied CPM to investigate individual variation in heterogeneity of murine lung cells during in vivo influenza virus infection, revealing that the relations between cell quantities and clinical outcomes varies in a gradual manner along the cellular activation process. Validation experiments confirmed these gradual changes along the cellular activation trajectory. Additional analysis suggests that clinical outcomes relate to the rate of cell activation at the early stages of this process. These findings demonstrate the utility of CPM as a mapping deconvolution tool at single-cell resolution, and highlight the importance of such fine cell landscape for understanding diversity of clinical outcomes. Lungs gene expression of Collaborative Cross mice taken 48h after the infection with either the influenza virus or PBS.