Novel Drivers of alpha-1A Adrenergic Receptor-mediated Heart Failure Identified through Correction for Cell-Type Shifts in Bulk Cardiac Transcriptomes

We have implemented an algorithmic approach that uses snRNAseq datasets as a reference to accurately calculate cell type compositions from bulk RNAseq datasets through robust data cleaning, gene selection, and multi-sample cross-subject and cross-cell-type deconvolution. We applied our approach to cardiomyocyte-specific alpha 1A adrenergic receptor (CM-alpha 1A-AR) knockout mice. 8-12 week-old mice (either WT or CM-alpha 1A-KO) were subjected to permanent left coronary artery (LCA) ligation or sham surgery (n=4 per group). Transcriptomes from the infarct border zones were collected 3 days later and analyzed using our algorithm to determine cell-type abundances and corrected differential expression calculated using DESEQ2 and validated using RNAscope.