Fig. 3: Altered expression levels of RNA binding proteins in SAH and AC induce unique alternative splicing changes.

Scatter plot showing a correlation between gene expression and gene accessibility in a SAH vs unaffected hepatocytes and b Hepatocytes vs Kupffer cells, indicating that gene accessibility changes strikingly correlate with cell type-specific gene expression changes but not with pathogenic cell-state transitions. c Examples of concordance and discordance between gene accessibility and expression between SAH and unaffected hepatocytes. d Heatmap showing expression of top enriched RBPs across unaffected, SAH, and AC patients. e Western blot images and f corresponding quantification demonstrating protein expression levels of various developmentally regulated RBPs from human livers (n = 4 biological replicates). g Venn diagram showing the intersection of misregulated alternative splicing events in SAH and AC. h Distribution of alternative splicing events in SAH and AC patients. i Distribution of RNA binding motifs for developmentally regulated alternative splicing factors around AS events. In (f), individual data points report biological replicates, and centers and error bars represent mean and Standard deviation, respectively. Blots in (e) are a representative image of 3 individual western blot trials. Two-way ANOVA statistical test used in (f). In (i), Fisher’s exact test was used with correction for False discovery rate and a cutoff of q < 0.05. SAH severe alcohol-associated hepatitis, AC alcohol-associated cirrhosis.