Figure 5.

HFD affects immunity, lipid metabolism, and liver translation in a sex- and strain-dependent manner

(A) Scheme of gene set enrichment analysis based on variance explained by diet, sex, and their interaction. (1) For each transcript, we computed the variance explained based on a linear model of strain, sex, diet, and their interactions (Transcript ∼ Strain + Diet + Sex + Diet:Sex). Then the percentage of variance explained of each transcript was assigned to specific parameters (diet, sex, and their interactions); (2) for ranking of the genes; and then (3) to perform gene set enrichment analysis for each parameter.

(B) Results of gene set enrichment analysis based on variance explained by diet, sex, and their interaction. From left to right, each enrichment was performed on gene ontology of biological processes (GOBP), cellular component (GOCC), and transcription factors. Percentage of variance explained was measured using variantPartition package.

(C) Enrichment analysis of the diet effect on liver gene expression separated by sex and strain. Gene set enrichment analysis was performed on the sign (log₂ (FC)) ∗ –log₁₀ (adjusted p value) per strain per sex. The selected gene sets add the highest score for the global response to the diet in a specific sex. GSEA permutation test; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001; adjusted p value corrected for multiple testing with the BH-FDR procedure.