Volume 128, Issue 5, Pages 1437-1444 (May 2005) Hepatic Gene Expression Discriminates Responders and Nonresponders in Treatment of Chronic Hepatitis C Viral Infection  Limin Chen, Ivan Borozan, Jordan Feld, Jing Sun, Laura-Lee Tannis, Catalina Coltescu, Jenny Heathcote, Aled M. Edwards, Ian D. McGilvray  Gastroenterology  Volume 128, Issue 5, Pages 1437-1444 (May 2005) DOI: 10.1053/j.gastro.2005.01.059 Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 1 Real-time PCR verification of genes predicted to be altered by microarray. Real-time PCR verification was performed as described in Materials and Methods. In all cases, 4 genotype 1 R samples were compared with 4 genotype 1 NR samples and 3 normal liver samples (white, normal; gray, R; black, NR). Values along the y-axis represent the ratio, in arbitrary units, of a given gene versus β-actin. Data are expressed as mean ± SEM. *P < .05 NR versus R; Welch t test. OAS-3, P = .054; CEB-1, P = .105; RPS28, P = .053; STXBP5, P = .12. Gastroenterology 2005 128, 1437-1444DOI: (10.1053/j.gastro.2005.01.059) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 2 Hierarchical cluster analysis using the 20 genes present in all 31 samples. Unsupervised hierarchical cluster analysis was performed as described in Materials and Methods, restricting the analysis to the 18 genes in Table 2. Red denotes an increase and green a decrease when compared with the reference RNA pool. An asterisk denotes the patients who experienced a relapse following treatment with pegylated IFN-α plus ribavirin. Note that normal liver tissue coclusters with patients who respond to treatment, while all NR samples form part of a discrete cluster. Gastroenterology 2005 128, 1437-1444DOI: (10.1053/j.gastro.2005.01.059) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 3 Cluster and classifier analysis using the 8-gene predictor set: all patients. (A) Hierarchical cluster analysis of all samples, restricting the analysis to the 8 genes in the predictor set. (B) KNN, LDA, and PCA of all samples using the 8-gene predictor set. Unsupervised (hierarchical cluster, PCA) and supervised (KNN, LDA) analyses were performed as described in Materials and Methods. As in Figure 2, an asterisk denotes treatment relapsers. Gastroenterology 2005 128, 1437-1444DOI: (10.1053/j.gastro.2005.01.059) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 4 Cluster and classifier analysis using the 8-gene classifier set: patients with genotype 1 infection only. A hierarchical cluster analysis of the 23 genotype 1 samples, restricting the analysis to the 8 genes in the predictor set. (B) KNN, LDA, and PCA of genotype 1 samples using the 8-gene predictor set. Unsupervised (hierarchical cluster, PCA) and supervised (KNN, LDA) analyses were performed as described in Materials and Methods. As in Figure 2, an asterisk denotes treatment relapsers. Gastroenterology 2005 128, 1437-1444DOI: (10.1053/j.gastro.2005.01.059) Copyright © 2005 American Gastroenterological Association Terms and Conditions