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SJIA flare signature analysis

Antibody array profiling. Plasma biomarker analysis (NSC, LDA, ROC). Urine profiling. Urine biomarker analysis (NSC, LDA, ROC). SJIA flare signature analysis. Classification. SJIA flare signature analysis. Classification. 5. 6. 4. 3. 2. 1. Discovery set (SAF, QOM).

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SJIA flare signature analysis

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  1. Antibody array profiling Plasma biomarker analysis (NSC, LDA, ROC) Urine profiling Urine biomarker analysis (NSC, LDA, ROC) SJIA flare signature analysis Classification SJIA flare signature analysis Classification 5 6 4 3 2 1 Discovery set (SAF, QOM) Discovery set (ND.SAF vs. AF.QOM.RD.KD.FI) LCMS raw spectra Biomarker identification 6 protein biomarker panel 14 peptide biomarker panel Peak finding peak alignment feature extraction NSC feature selection NSC feature selection LDA analysis 43 protein antibodies LDA analysis Feature selection Feature selection Ten-fold Cross-validation Ten-fold Cross-validation “bootstrap” samples SAF vs. QOM Training Samples SAF vs. QOM ND.SAF vs. KD.FI ND.SAF vs. QOM.RD Urine peptide index Antibody array assay ROC analysis 500 bootstrap samples ROC analysis FIGURE 1

  2. TABLE 1

  3. TABLE 2

  4. TABLE 3

  5. U test P value Protein m/z Peptide sequence ND/SAF vs. KD/FI ND/SAF vs. QOM/RD A1AT 1796.96 2.07E-03 3.19E-04 EAIPMSIPPEVKFNKP A1AT 1945.98 6.38E-04 8.68E-05 EAIPMSIPPEVKFNKPF COL1A1 1570.73 1.52E-03 2.52E-01 GAKGDAGApGApGSQGApG COL1A1 1580.707 9.84E-07 1.12E-03 SpGSpGPDGKTGPPGpAG COL1A1 1734.8 3.03E-02 1.80E-01 GPpGPpGKNGDDGEAGKPG COL1A1 1810.89 3.89E-02 6.87E-02 GPpGKNGDDGEAGKpGRpG COL1A1 2408.07 1.52E-03 1.20E-02 NGDDGEAGKPGRpGERGPpGP COL1A2 1853.79 1.58E-01 5.63E-02 NGApGEAGRDGNpGNDGPpG COL3A1 1624.73 6.38E-04 1.00E-01 DGApGKNGERGGpGGpGP COL9A2 1126.49 9.84E-07 8.59E-03 PpGPpGYPGKQ FGA 1826.79 3.50E-02 1.25E-01 DEAGSEADHEGTHSTKR FGA 1883.797 2.81E-04 4.26E-03 DEAGSEADHEGTHSTKRG FGB 1631.83 3.17E-04 6.55E-02 EEAPSLRPAPPPISGGG FGB 1794.9 6.51E-03 5.08E-04 EEAPSLRPAPPPISGGGY THP 982.58 3.87E-07 1.30E-01 VLNLGPITR THP 1654.91 3.56E-01 6.23E-02 SGSVIDQSRVLNLGPI THP 1755.95 2.34E-04 1.30E-01 SGSVIDQSRVLNLGPIT TABLE 4

  6. A B C Classification ND SAF KD FI Clinical diagnosis ND.SAF KD.FI Sensitivity 2+18 23+23 n = Predicted probabilities LDA Predicted as SJIA F 17 0 Predicted as non SJIA F 3 46 Mean(AUC): 99.9% Percent Agreement with clinical diagnosis 85% 100% + - 95.5% Overall P = 4.53X10-13 1- Specificity Patient samples FIGURE 2

  7. A B C Classification ND SAF QOM RD Clinical diagnosis ND.SAF QOM.RD Sensitivity 2+18 18+9 n = Predicted probabilities LDA Predicted as SJIA F 18 0 Predicted As SJIA Q 2 27 Mean(AUC): 99.8% Percent Agreement with clinical diagnosis 90% 100% + - 95.7% Overall P = 4.16X10-11 1- Specificity Patient samples FIGURE 3

  8. ENBREL ANAKINRA CR PR CR Predicted probabilities Patient samples FIGURE 4

  9. Relative abundance AF.QOM.RD.KD.FI Protein MH+ Sequence ND.SAF -0.0004 -0.024 -0.0787 -0.1467 -0.0009 -0.0352 0.0015 0.0986 0.3225 0.6016 0.0037 0.1443 FGA(20-35) 1536.61 ADSGEGDFLAEGGGVR FGA(607-622) 1639.77 AGSEADHEGTHSTKRG FGA(605-621) 1826.80 DEAGSEADHEGTHSTKR FGA(605-622)1883.80 DEAGSEADHEGTHSTKRG FGA(605-628) 2560.2 DEAGSEADHEGTHSTKRGHAKSRP FGA(605-629)* 2659.24 DEAGSEADHEGTHSTKRGHAKSRPV TABLE 5

  10. FGA peptide marker distribution FGA(605-621) 1826.80 FGA(20-38) 1536.69 FGA(605-622) 1883.80 FGA(607-622) 1639.77 Relative abundance FGA(605-629)* 2659.24 FGA(605-628) 2560.2 FIGURE 5 ND SAF QOM AF RD KD FI HC ND SAF QOM AF RD KD FI HC

  11. I II III IV V VI VII TABLE 6

  12. A B C Training samples n = 39 Bootstrapping samples n = 52 SJIA SJIA Clinical diagnosis Clinical diagnosis F Q F Q 25 14 41 11 n = n = LDA Testing Classified as F Classified as F 23 4 36 2 Classified as Q Classified as Q 2 10 5 9 92% 71.4% 87.8% 81.8% - - Percent Agreement with clinical diagnosis Percent Agreement with clinical diagnosis + + 84.6% 86.5% Overall P = 7.9X 10-5 Overall P = 2.4 X 10-5 FIGURE 6

  13. D Training Bootstrapping testing SAF QOM SAF QOM Predicted probabilities Patient samples FIGURE 6

  14. Sensitivity Sensitivity Training Bootstrapping testing Mean(AUC): 92.2% Mean(AUC): 90.7% 1- Specificity 1- Specificity FIGURE 7

  15. Overlapping Samples Urine Samples Plasma Samples 74 3 63

  16. Overlapping Patients Urine Patients Plasma Patients 24 13 13

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