IRF8^K108E mutation modifies global gene expression profile of blood cells. (A) RNA extracted from PBMCs of 5 healthy individuals and from the IRF8^K108E patient were sequenced (RNA-seq). The expression level of significantly dysregulated genes in the K108E sample, shown as Log2 of sequence read CPM, are presented in a heatmap together with the expression level of the control samples. There are 724 genes that exhibit increased and 694 genes that have decreased expression in the K108E PBMCs sample. The number of IRF8 binding sites found in the vicinity of each dysregulated gene is represented by blue bars. For the 2 groups of genes, a graph shows the cumulative number of IRF8 binding sites found in proximity of these genes in chromatin from activated macrophages. (B) GO enrichment analysis of genes that show either increased (yellow) or decreased (blue) expression in K108E compared with controls; the degree of statistical significance is shown. (C) The K108E expression profile was subjected to GSEA³⁹  to identify specific immune cell signatures either overrepresented or depleted in K108E compared with controls. Immune cell signatures were produced by pairwise comparisons of public data sets (see “Materials and methods”) and are indicated on top of each graph. GSEA graphs illustrate the cumulative enrichment score in each specific gene signature comparison; the occurrence of the cell signature genes is identified as individual black lines over the distribution of the K108E patient gene profile. Normalized enrichment scores (NES) and false-discovery rate (FDR) are shown for each displayed analysis.