Figure 2.

Associations of the liver transcriptome gene expression with the circulating histidine levels

(A) Volcano plot of differentially expressed gene transcripts associated with the plasma histidine levels in the discovery cohort (n = 88), identified using robust linear regression controlling for age, BMI, gender, and country. The log₂(FC) associated with a unit change in the plasma histidine levels and the −log₁₀(p value) adjusted for multiple testing are plotted for each transcript.

(B) Dot plot of the results of the Reactome-based over-representation analysis performed on active subnetworks grouped by hierarchical clustering. The x axis represents the fold enrichment defined as the ratio of the frequency of input genes annotated in a pathway to the frequency of all genes annotated to that pathway. The dot size indicates the number of differentially expressed genes in a given pathway. Dots are colored by the −log₁₀(p_FDR), with red indicating higher significance.

(C) Enrichment map inter-related significant pathways identified using an active subnetwork-oriented approach. Each color displays a cluster of related pathways using a threshold for kappa statistics of 0.35. The size of the nodes corresponds to its −log₁₀(p_FDR). The thickness of the edges between nodes corresponds to the kappa statistic between the two nodes.

(D) Gene concept network depicting significant genes involved in enriched pathways from selected clusters. The dot size of the pathways represents the −log₁₀(p_FDR). Pathways with the same color correspond to the same cluster.