The PWK/PhJ transcriptional response to WD-TN recapitulates changes seen in human NASH. (A) Diagram of the bioinformatic pipeline. Differential expression analysis is performed on mouse and human RNA-seq data and transcriptional changes are characterized by logFC-ranked GSEA and by ORA on overlapping significantly DEGs. (B) Volcano plot of DEGs (NAS ≥ 4 vs. NAS < 4) for the two human liver datasets. Numbers indicate the significant up-/downregulated genes. Red line indicates significance threshold (Benjamini–Hochberg adjusted P value = 0.05); gray indicates non-DEGs; green indicates genes significantly up- or downregulated in both human datasets. (C) Direction-specific percentage of human DEGs overlapping in the two human datasets, their overlap, and in each of the seven strains. (D) Representative ORA-enriched gene sets for the upregulated gene groups defined in C. Gray indicates missing value. (E) Representative ORA-enriched gene sets for the downregulated gene groups defined in C. (F) ORA of liver-specific cell type enrichment for the upregulated gene groups defined in C. Every row represents a gene set for a cell type sub-population. (G) Representative GSEA-enriched gene sets. (H) Cell type GSEA enrichment results. Rows represent gene sets for cell type sub-populations. For all panels: C57BL/6J-CD n = 8, C57BL/6J-WD n = 8, DBA/2J-CD n = 6, DBA/2J-WD n = 7, A/J-CD n = 6, A/J-WD n = 6, 129S1/SvlmJ-CD n = 7, 129S1/SvlmJ-WD n = 7, WSB/EiJ-CD n = 6, WSB/EiJ-WD n = 6, CAST/EiJ-CD n = 8, CAST/EiJ-WD n = 8, PWK/PhJ-CD n = 6, PWK/PhJ-WD n = 7. Each group of mice was assayed in two independent cohorts. FDR-corrected P values: *, q < 0.05; **, q < 0.01; ***, q <0.001. BP, GO-BP; MC, mitocarta; RM, reactome; HK, Hallmark; KG, KEGG; WP, WikiPathways; reg., regulation; (+), positive; (−), negative; GF, growth gactor; Int., interferon; Sig., signaling; epith., epithelial; Cs, cells; Bile D, bile duct; BA, bile acid, ECM, extracellular matrix.