Fig. 1: Multiomic profiling of human alcohol-associated liver diseases.

a Schematic summarizing single nuclear isolation from human liver samples and transcriptomics using multiomic and deep sequencing approaches. (Created in BioRender. Das, D. (2025) https://BioRender.com/mskjuhf). b rnaUMAP showing distinct cell populations identified from multiomic profiling at single-cell resolution from over 27,000 liver nuclei from 15 individuals (n = 5 each). c Distribution of various liver cells in unaffected and alcohol-associated liver disease (ALD) patients. AC and SAH showed an increased number of non-hepatocyte (NPC) cells. Non-directional Chi-squared test was performed cell numbers showed a p-value < 0.0001, indicating statistically significant change in cell populations depending on conditions. d Distribution of porto-central coordinate \({\eta }_{i}\) values in unaffected liver, AC, and SAH conditions. The histogram shows the frequency of cells at different \({\eta }_{i}\) values for each condition, followed by p-value from using two-sided Kolmogorov–Smirnov (K–S) test, which shows significant differences (p < 0.05) between unaffected and diseased distributions. e Cell type-specific changes in gene expression associated with ALD (examples shown in dot plot, left) and corresponding gene ontology analysis demonstrating affected processes (right). f Average Transcript per million (TPM) values of key pro-inflammatory cytokines as quantified from bulk RNA-seq. Correspoding Average TPM values are shown within each box of the heatmap. SAH severe alcohol-associated hepatitis, AC alcohol-associated cirrhosis.