IgG and IgM binding was measured for all samples for each peptide and the z score for each peptide calculated for each rheumatoid arthritis group (CCP+RF+, CCP+RF-, CCP-RF+, and CCP-RF-) compared to control. The proportion (y axis) of z scores less than the specific z value on the x axis was graphed as an empirical cumulative distribution function (ecdf) plot. The median z score for each rheumatoid arthritis group is where its ecdf curve crosses the dotted line at 0.5. Statistical significance was assessed by permutation analysis. A. Citrulline-containing peptides and citrulline-specific binding (binding values for citrulline-containing peptides minus corresponding arginine-containing peptides), n=35,459 peptides or peptide pairs. B. Homocitrulline-containing peptides and homocitrulline-specific binding (binding values for homocitrulline-containing minus corresponding lysine-containing peptides), n=41,608 peptides or peptide pairs. C. All native peptides and native peptides excluding peptides with arginine or lysine, n=95,761 native peptides, 18,694 native peptides without arginine or lysine. For all panels, n=12 samples per group, p<0.0001 for all comparisons despite some small visual differences, except citrulline-specific IgM binding for CCP-RF+ versus control, which was not significant.