Classifier training FDR analysis Predictor discovery in training set 4 Training set SJIA (12 F, 12 Q) 1 DIGE raw gel images Matched samples SJIA (10 F, 10 Q) POLY (5 F, 5 Q) Spot finding spot alignment feature extraction Classifier training Classify SJIA F vs Q DIGE analysis Prediction analysis (LDA) Predictor test in testing set 5 Testing set SJIA (10 F, 10 Q) 2 Cluster analysis 2d hierarchical clustering heatmap plotting Normalization manual review Manual review MSMS Protein ID 3 15 protein 2d clustering 12 ELISA Assay development Feature selection 7 Discriminate SJIA F KD FI Supplementary Figure 1 Clustering Box-and-Whisker Analysis Discriminate SJIA F SJIA Q POLY F POLY Q ELISA assays 7 ELISA assay ELISA assay FI (27 ) KD (10) 9 ELISA assay Q->F (5) Q->Q (10) Test to anticipate SJIA F in Q LDA Fisher exact test randomization Blind testing Classify SJIA F vs Q Fisher exact test SJIA F(12) FI (15) Classify SJIA F vs FI Fisher exact test

numberspot label Protein biomarker 11 (a,b)APO-AI 22GSN 33TTR 44FGB 55FGG 66APO-D 77APO-E 88 (a,b)ATIII 99 (a,b)A2M 1010 (a,b)CFH 11 VDB 12 KLKB (a,b)AMBP 14 APO-AIV 15 APO-L 1616 (a,b,c)C (a,b)C9 18 CRP 1919 (a,b,c)HP 20 S100A9 21 S100A (a,b)SAA 23 SAP 24 ACT 25 AGP1 26 C3 Supplementary Figure 2 pH MW/ anti-trypsin 2 albumin 3 serrotransferrin 4 Ig heavy chain 5 Haptoglobin 6 Ig light chain Removed proteins: Patient 1 and Patient 2 whole plasma Patient 1 and Patient 2 after protein depletion AB Hemoglobin

Figure 1 FQ SJIA APOA1 GSN APO-D APO-E ATIII A2M ATIII CFH TTR VDB KLKB1 AMBP APO-L1 APO-IV C4 C9 CRP HP S100A9 S100A8 SAA SAP AGP1 C3 ACT FGG FGB

SAA S100A9 S100A8 CRP HP SAP APO IV ACT AGP1 C4 GSN A2M APO A1 CFH TTR Figure Number of features called significant False discovery rate (FDR) FQ SJIA FQ POLY KD SJIA FFI SJIA F P value: 1.1 E -4P value: 0.5P value: 0.19P value: 1.4 E -4 AB

Goodness of class separation –  probability SJIA TrainingSJIA Test Feature# Figure 3