Fig. 1

Widespread gene expression changes in ALS post-mortem brain. (a) The five brain regions examined by RNA sequencing for 22 sporadic ALS patients and 11 controls (n = 165 samples). According to the staging scheme, motor cortex presents with pTDP-43 inclusions in stage 1, 2, 3 and 4 ALS patients, prefrontal cortex presents with pTDP-43 inclusions in stage 2, 3 and 4 ALS patients, hippocampus presents with pTDP-43 inclusions in stage 4 ALS patients, and cerebellum and occipital cortex rarely present with pTDP-43 pathology. (b) Volcano plots showing the genes that were significantly upregulated (in red) or downregulated (in blue) in the ALS patients relative to controls (FDR < 0.05). Dashed lines indicate the boundary for a 2-fold increase and decrease in gene expression. Genes that have been genetically implicated in ALS, and which were significantly differentially expressed, are labelled. (c) Gene set enrichment analysis result for the MSigDB human hallmark gene sets. Tiles are coloured by the normalised-enrichment score (NES) indicating whether a particular gene set was enriched or depleted in ALS patients relative to controls. P-values are adjusted using the Benjamini Hochberg method (*, adjusted p-value < 0.05; **, adjusted p-value < 10^− 3; ***, adjusted p-value < 10^− 5). MC, motor cortex; FC, prefrontal cortex; HP, hippocampus; OC, occipital cortex; CB, cerebellum