Fig. 4
ALS CSF protein network changes are preserved in a larger multicenter cohort. a. Schematic of experimental workflow to quantitatively evaluate an additional CSF proteome generated DIA-MS (multicenter dataset), indicating sample size and number of proteins quantified. Note the addition of an asymptomatic SOD1-mutation group. b. Scatter plot showing the overlap in effect size in the subset of individuals included in both TMT-MS and DIA-MS (N = 50, C9orf72 = 10, Control = 40). Proteins that varied significantly in both sets were compared using BiCor and associated Student correlation p-value. The number of proteins in each quadrant is denoted by “n”. c. Module preservation of TMT-MS (original dataset) and DIA-MS (expanded dataset). Number of proteins in each module (x-axis) is compared across Zsummary and overall measurement of preservation, (y-axis). The red line at Zsummary = 10 (q = 1 × 10–23) indicates TMT-MS modules are highly preserved in the replication proteome. The blue line at Zsummary = 2 (q = 0.05) indicates TMT-MS modules are preserved in the DIA-MS dataset. d. Scatter plot correlating module eigenproteins for C9orf72 vs. control for TMT-MS (y-axis) and DIA-MS (x-axis). 10 of 12 network modules correlate between the two methods. Synthetic eigenproteins were constructed for DIA-MS dataset and measured by disease type in TMT-MS datasets. A minimum of four proteins from the top 20% of module membership by kME (correlation to module eigenprotein) were used to assess synthetic eigenprotein value (y-axis) and compared across disease type (x-axis) (Supplemental Table 11)