Discovery phase data analysis
(A) Discovery phase data quality and statistical analysis workflow (N = 46). Sequential pre-filtering steps focused on identification and removal of high-variability (steps 1–2) and low-coverage (step 3) peptides and proteins. Resulting proteins and peptides were submitted to multiple statistical comparisons in the context of autoimmunity and T1D development (steps 4–5).
(B) Functional enrichment analysis. The 376 differentially abundant proteins identified from the discovery phase were submitted to function enrichment analysis with DAVID using the KEGG annotation. Pathways were plotted as circles, with sizes based on their fold enrichment and colors based on p values. Individual pathways were grouped into larger biological processes based on the overlapping proteins between each pathway. Pathways that were also enriched among the 167 targets of the validation phase are marked with asterisks. Comparison I1: time point(s) before seroconversion of the group that remained in autoimmunity by the age of 6 years (IA group) paired against matched controls. Comparison T1: time point(s) before seroconversion of the group that developed T1D by the age of 6 years (T1D group) paired against matched controls. Comparisons I2 and T2 have the same group of individuals as I1 and T1, respectively, but after seroconversion. Comparisons I3 and T3 compare IA and T1D groups before vs. after seroconversion, respectively.