The alternative splicing landscape of infarcted mouse heart identifies isoform level therapeutic targets. The alternative splicing landscape of infarcted mouse heart identifies isoform level therapeutic targets

Alternative splicing is an important process that contributes to highly diverse transcripts and protein products, which can affect the development of disease in various organisms. Cardiovascular disease (CVD) represents one of the greatest global threats to humans, particularly acute myocardial infarction (MI) and subsequent ischemic reperfusion (IR) injury, which involve complex transcriptomic changes in heart tissues associated with metabolic reshaping and immunological response. In this study, we used a newly developed ONT full-length transcriptomic approach and performed transcript-resolved differential expression profiling in murine models of MI and IR. We built an analytical pipeline to reliably identify and quantify alternative splicing products (isoforms), expanding on the currently available catalog of isoforms described in mice. The updated alternative splicing landscape included transcripts, genes, and pathways that were differentially regulated during IR and MI. Our study establishes a pipeline to profile highly diverse isoforms using state-of-the-art long-read sequencing, builds a landscape of alternative splicing in the mouse heart during MI and IR. Overall design: Cardiac tissue was sampled from myocardial infarction and ischemia-reperfusion mice, and sham-operated controls were set up separately. Using different sequencing methods, novel transcripts were identified and pairs of differential transcripts and genes were investigated. Please note that Nanopore-based long-reads data (GSM8486343-GSM8486346) were used to identify novel transcripts and genes, therefore there is no coresponding data columns in the raw_count_gene.tsv and tpm_transcript.csv files.