PCA of variables measured in this study. Active variables for this PCA were: percentage of motor neurons containing granular SOD1 (MN_granular_disSOD1), SOD1 inclusions (MN_disSOD1), granular CCS (MN_granular_CCS) and diffuse cytoplasmic CCS (MN_diffuse_CCS), motor neuron density (neuronal_density), total (SOD1_act) and specific SOD1 activity (SOD1_spec_act), SOD1 (SOD1 level) and CCS protein levels (CCS level), Cu:Zn atomic ratio within enzymatically active soluble mature SOD1 (SOD1_CuZn_ratio), active SOD1 pI (pI), GSH levels (GSH) and copper and zinc levels in whole tissues (Total_Cu, Total_Zn), as well as soluble (Soluble_Cu, Soluble_Zn) and insoluble tissue extracts (Insoluble_Cu, Insoluble_Zn). SOD1 PTM data were also included, although these were grouped on the basis of similarities in expected functional consequences; PTMox—oxidation His, Trp, Cys, nitration Trp; PTMch—acetylation Lys, Phosphorylation Ser; PTMdeam—deamidation Asn; PTMage—CEL Lys; GlyGly_Lys91. Each point represents a sample of ventral spinal cord (VSpC) sample in this study—that is, each dot expresses every measurement obtained for that particular sample as a single value in two-dimensional space. Large dots with coloured ellipses represent the centroid for that category or grouping and its 95% confidence interval. (A) PCA plot of SOD1-fALS (green), non-SOD1-fALS (orange), sALS (red) and control (blue) cases across dimension 1 (x-axis), dimension 2 (z-axis) and dimension 3 (y-axis). (B–D) The percentage contribution of the top 10 most influential variables comprising dimensions 1–3. The mean percentage contribution of all variables to each dimension is indicated by a red dotted line. (E) PCA plot of ALS cases grouped according to site of onset; bulbar (blue) or limb (red).