Fig. 5
Association of up-DPpGCs with ALS proteome changes and ALS risk genes. A Venn diagram displaying intersections of DPpGCs up-produced in ALS with NHGRI-EBI Catalog of human GWAS, Harmonizome database, and the ALS DEPs. B Overlap of DPpGCs (blue) with proteomic DEPs (green) and GWAS ALS risk gene annotations (purple). In total, 28.0% of DPpGC related genes conveyed an ALS risk in GWAS, and 18.7% showed a DEP pendant; an additional ALS risk annotation for those with DEP partner was found for 45.2%. C Pair-correlation of DPpGCs and DEPs in ALS. Out of the 225 DPpGCs, 42 showed altered protein abundance. While all DPpGCs were up-produced, DEPs were up- or down in content. DPpGCs with strongest up-regulation (large dot diameters) predominantly showed discordant DEP regulation (blue in color code). Up-DPpGCs and DEPs are illustrated in red; down-regulated DEPs are marked in blue. sNE soluble nuclear fraction, cNE chromatin-bound nuclear fraction, Cysk cytoskeletal fraction, CP cytoplasmic fraction, ME membrane fraction. n = 9 for DPpGCs; n = 5 for DEPs. p-value for DPpGCs ≤ 0.01; q-value for DEPs < 0.05. Threshold average log2 ratio for DEPs > 0.38. D Percentages of DPpGCs pair-correlated with DEPs in the 5 proteomics fractions in ALS. E Cellular functions of the 42 DPpGC—DEP tandems, according to GeneCards (https://www.genecards.org/cgi-bin/carddisp.pl?gene). Pairs conveying neuronal and ALS-counteracting functions were primarily down-regulated (blue on color bar), while those mediating a more general cell biology were up-regulated (red on color bar). Some functional categories were either up- or downregulated in the different cellular subfractions (purple on color bar). F Color-encoded in the map are the cell types with enriched expression of the individual genes, as assessed from the Human Protein Atlas. The cell type with clustered expression is indicated in the heading. White background color indicates no clustering. NEU, neurons, OLG, oligodendrocytes; AST, astrocytes; MIC, microglia; SM, skeletal muscle cells