Extended Data Fig. 2: Comparison of structural features of variable and non-variable peptides, and the proteins containing these peptides, in CSF.
a, Distribution of secondary structures as loops, alpha-helix and beta-strands for variable/non-variable peptides, as predicted using PSIPRED. Boxplots for all panels: median, center; first and third quantile, lower and upper hinges; largest/smallest value no further than 1.5 * inter-quantile range of the hinge, whiskers; data points beyond are defined as outliers and plotted individually. P values are indicated (Wilcoxon rank sum test; ns, not significant; 9385 non-variable, 386 medium-variable, 117 high-variable peptides, from 51 subjects) b, c, Predicted propensity of peptides to bind DNA or RNA. d, Predicted solvent accessible surface area of variable/non-variable peptides. e, Number of high confidence interaction in STRING for proteins with at least one highly variable peptide (red), as compared to all other proteins (gray). f, g, Sequence length and number of domains as annotated in the PFAM database for proteins with at least one highly variable peptide (red), as compared to all other proteins (gray). h, Side-by-side view of affected peptides from in situ (left, reproduced from Fig. 2g for comparison) and in vitro experiments (right). Structure of human brain fructose bisphosphate aldolase (PDB entry 1XFB). The enzyme is a homotetramer, one subunit is shown as light blue cartoon and the other 3 subunits are shown as gray surface. The substrate is represented as yellow spheres, based on an alignment of PDB entry 1XFB with the ligand bound structure of the muscle isoform (PDB entry 4ALD). For the in situ data (left), the highly variable peptides are highlighted in dark red (bimodal) and salmon (unimodal). For the in vitro data (right), the significant peptides in the presence and absence of fructose 1,6-bisphosphate are highlighted in red (log2 fold change < −1 or > 1). The bimodal and non-bimodal peptide identified in situ are encircled. Numerical data for graphs in a-g are available as source data.
