Transcriptomic signatures between HIV-infected putative progressors and viremic non-progressors.

Gene expression profiles from whole blood were assayed by microarray analysis. (A) Prinicipal components analysis was used to assess the divergence of the entire transcriptomic profile of the patient classes. (B) Volcano plot showing the distribution of fold-changes and significance level between the PP and VNP phenotypes and the p-value assessed by two-sample t-test. Red data points indicate genes upregulated in PP patient samples, defined as >1.5-fold greater than the VNP samples, and a p-value of <0.05. Blue data points indicate genes >1.5-fold in VNPs with 0.05 p-value. The y-axis is plotted as the log of the inverse of the p-value. (C) Pathway analysis of genes differentially expressed between VNPs and PPs was performed using the Gene Ontology database. Fisher's exact test was used to estimate the significance of enrichment an annotations of probesets on the arrays were used as a background. The forest plot shows genes identified by GO as have immune function and divides them into GO subcategories. (D) Heat map showing the overall concordance amongst patients in each class. The top 50 most highly expressed genes were median-normalized and organized by hierarchical clustering using Pearson's dissimilarity metric and average linkage. (E) Forest plot of 52 genes defined in the GO category “Immune Process” in panel C. Branches indicate subcategories, the number of genes with higher expression in each phenotype are indicated by the scale on the x-axis, and the magnitude of the fold-change is indicated by the color scale. (F) Relative expression of ISGs between phenotypes. (G) Forest plots of individual genes contained with GO categories and unincorporated immune genes. *probeset is predicted to hybridize to multiple genes. (H & I) Gene Set Enrichment plots of ISGs and IL6 signaling genes. GSEA performed using geneset permutation, and array data ranked by signal-to-noise ratio. Vertical dotted lines indicate the margin between gene upregulated in VNPs (left) and PPs (right) of all non-redundant, annotated genes on the array. Data points in red indicate leading edge genes contributing to the majority of the enrichment score.