Serial changes in expression of functionally clustered genes in progression of liver fibrosis in hepatitis C patients

Figure 1 Clusters of genes in functional categories. The characteristic behavior of gene clusters for each functional category is shown separately in Figure 1A-I. The numbers in each figure refer to the serial number of genes in Table 1. The expression ratio relative to the F1 stage is plotted in each graph. A: Inflammation gene cluster with a peak at F2; B: ECM gene cluster showing increased expression along with fibrosis progression; C: Insulin/Wnt signaling gene cluster with increased expression in the early phase of fibrosis; D: Blood coagulation factor gene cluster showing decreased expression along with fibrosis progression; E: Lipid metabolism gene cluster showing decreased expression along with fibrosis progression; F: Sulfurcontaining amino acid metabolism gene cluster showing a synchronous decrease in expression from F2 to F3; G: Two transcription factor gene clusters showing sequential decreases in expression; H: Insulin/Wnt signaling gene cluster showing decreased expression from F2 to F3; I: A gene cluster showing a peak or bottom at F3.

Figure 2 Comparison between statistical clustering analysis and functional cluster. All genes in Figure 1 were subjected to hierarchical clustering analysis using Genowiz™. Statistical clustering of the expression ratio between neighboring F stages for the genes in Table 1 was combined with functional categories. The color coding in the center column shows the expression ratio between neighboring F stages for the genes in Table 1: Ratio increases from green to red. The left dendrogram shows the result of hierarchical clustering by Genowiz™ software. The numbers on the right of gene names indicate the subgraph numer in Figure 1, which represents functional categories, and the same numbers are tied with color bars.

Figure 3 Molecular network associated with lipid metabolism. Gene expression changes in pathways related to lipid metabolism, illustrated with bioSpace Explorer (a system for analysis of DNA microarray data for lipid metabolism; Pharma Frontier Co. Ltd / World Fusion Co. Ltd.; see texts for details). The bird’s-eye view of the lipid metabolism is displayed. The up-regulated and down-regulated gene expression ratios at F3 vs F1 in Table 1 are displayed in red and green, respectively, with the color gradation proportional to the ratio. Genes in Table 1 that did not show a statistically significant change in expression are indicated with a blue circle with gray background. An entry with a gray background only indicates no input data. Most of the entity names in Figure 2 are the same as the gene name in Table 1, but the names “C20orf97”, “SCEH”, “Acaa2”, and “ACS5” in Figure 2 refer to “TRIB3”, “ECHS1”, “ACAA2”, and “ACSL5”, respectively, in Table 1. These differences are due to the software used in bioSpace Explorer.