Fig. 4
Transcriptomic profiling of WT and IDE-KO primary microglia. A Heatmap representation of the top 100 differentially expressed genes (DEGs) in IDE-KO vs. WT microglia (N = 2 individual microglial cultures/genotype). Clustering of genes by expression profile is shown on the left. B Volcano plot showing in red the genes that are differentially expressed (FDR < 0.05). C Gene enrichment analysis using the 103 DEGs. Manhattan plot on the left depicting functional terms grouped by data sources (X-axis) versus the adjusted enrichment p-values in negative log10 scale (Y-axis). Circle sizes are in accordance with the corresponding term size. Data sources: GO Gene Ontology (with three major categories: MF Molecular Functions, BP Biological Process, and CC Cell Component); Biological pathway databases (KEGG, REAC Reactome, and WP WikiPathways); regulatory motifs in DNA (TF Transcription Factors; MIRNA micro-RNAs), Protein databases (CORUM and HP Human Protein Atlas). The table on the right has the top 20 most significant GO terms, sorted by p-values. D Gene enrichment analyses performed separately in upregulated (left) and downregulated (right) DEGs in IDE-KO vs. WT microglia, showing the top 10 GO terms. The Rich Factor is calculated as the ratio between the number of target genes belonging to a pathway and the number of all annotated genes located in the pathway. The size of the dots indicates the number of target genes in the pathway, while dot's color reflects the different p-value range. E Validation of RNA-Seq data by qPCR using RNA from an independent pair of microglial cultures