SUPPLEMENTARY DATA Supplementary Figure 1. Flowchart of study population. IA Negative: individuals who were never persistently positive for any islet autoantibody; IA Positive: individuals who had one or more persistently positive islet autoantibodies; Type 1 diabetes: diagnosed by ADA criteria between 1994 and 2011; AbPos: Antibody positive group; T1D: type 1 diabetes group. ©2019 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-1263/-/DC1 SUPPLEMENTARY DATA Supplementary Figure 2. Description of Repeated Optimization for Feature Interpretation with Posterior Probability Product (ROFI-P3) Algorithm. ©2019 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-1263/-/DC1 SUPPLEMENTARY DATA Supplementary Figure 3. Average Area Under the Receiver Operating Characteristic Curve (AUC) based on 5-fold cross-validation repeated 100 times for each data source and machine learning classification method. Outlined by a box are the maximum average AUC values selected for each of the six datasets across seven machine learning algorithms for two disease stages: (A) seroconversion and (B) progression to diabetes. This was the optimal machine learning algorithm. Methods used: RF: Random Forest; KNN: K-Nearest Neighbors; LDA: Linear Discriminant Analysis; LR: Logistic Regression; SVM (RBF): Support Vector Machine with a radial basis function kernel, SVM (LIN): SVM with a linear kernel; and NB: Naïve Bayes. ©2019 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-1263/-/DC1 SUPPLEMENTARY DATA Supplementary Figure 4. Number of features from each data stream retained at 50% selection for (A) Development of IA and (B) Progression from IA to diabetes Data Stream Data Data Stream Data ©2019 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-1263/-/DC1 SUPPLEMENTARY DATA Supplementary Table 1. Raw data for age and islet autoantibody status for control, islet autoantibody positive (AbPos) and type 1 diabetes (T1D) groups. Age and islet autoantibody status (1=positive, 0=negative) are given for each time point. Serum autoantibodies were measured for insulin (IAA), glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A) and zinc transporter 8 (ZnT8A). Group randomID Timepoint Age (years) GADA IA-2A IAA ZnT8A Control 11010 T1 0.8 0 0 0 T2 3.0 0 0 0 T3 6.0 0 0 0 T4 12.0 0 0 0 Last 19.0 0 0 0 Control 13063 T1 0.8 0 0 0 T2 2.3 0 0 0 T3 4.3 0 0 0 T4/Last 6.8 0 0 0 0 Control 21580 T1 0.7 0 0 0 T2 7.5 0 0 0 T3 9.3 0 0 0 T4/Last 13.4 0 0 0 Control 21645 T1 0.7 0 0 0 T2 3.0 0 0 0 T3 5.2 0 0 0 T4/Last 8.2 0 0 0 0 ©2019 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-1263/-/DC1 SUPPLEMENTARY DATA Control 24684 T1 0.8 0 0 0 T2 2.1 0 0 0 T3 9.1 0 0 0 T4 12.1 0 0 0 Last 18.8 0 0 0 Control 28102 T1 0.7 0 0 0 T2 4.2 0 0 0 T3 7.6 0 0 0 T4/Last 16.1 0 0 0 Control 28410 T1 1.9 0 0 0 T2 5.1 0 0 0 T3 6.1 0 0 0 T4 7.2 0 0 0 0 Last 14.0 0 0 0 Control 31888 T1 0.7 0 0 0 T2 4.3 0 0 0 T3 6.3 0 0 0 T4 11.8 0 0 0 Last 19.2 0 0 0 Control 35055 T1 0.7 0 0 0 T2 3.0 0 0 0 ©2019 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-1263/-/DC1 SUPPLEMENTARY DATA T3 8.0 0 0 0 T4 16.0 0 0 0 Last 18.9 0 0 0 Control 38964 T1 0.8 0 0 0 T2 1.3 0 0 0 T3 2.1 0 0 0 T4 11.1 0 0 0 Last 18.5 0 0 0 Control 44935 T1 0.8 0 0 0 T2 2.0 0 0 0 T3 4.2 0 0 0 T4 6.9 0 0 0 Last 12.8 0 0 0 Control 51884 T1 1.2 0 0 0 T2 2.0 0 0 0 T3 3.1 0 0 0 T4/Last 4.1 0 0 0 0 Control 54642 T1 0.7 0 0 0 T2 2.0 0 0 0 T3 4.0 0 0 0 T4/Last 8.8 0 0 0 0 Control 57003 ©2019 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-1263/-/DC1 SUPPLEMENTARY DATA T1 1.3 0 0 0 T2 5.4 0 0 0 T3 11.5 0 0 0 T4 15.5 0 0 0 Last 17.5 0 0 0 0 Control 57732 T1 0.8 0 0 0 T2 1.3 0 0 0 T3 2.1 0 0 0 T4 3.1 0 0 0 0 Last 9.2 0 0 0 Control 61032 T1 0.9 0 0 0 T2 1.5 0 0 0 T3 2.0 0 0 0 T4 4.1 0 0 0 0 Last 16.3 0 0 0 Control 62568 T1 2.0 0 0 0 T2 4.5 0 0 0 T3 6.6 0 0 0 T4 7.6 0 0 0 Last 11.8 0 0 0 0 Control 66029 T1 1.2 0 0 0 T2 3.0 0 0 0 ©2019 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-1263/-/DC1 SUPPLEMENTARY DATA T3 7.1 0 0 0 T4 16.1 0 0 0 Last 23.0 0 0 0 Control 74515 T1 0.8 0 0 0 T2 3.2 0 0 0 T3 6.5 0 0 0 T4 12.1 0 0 0 Last 17.4 0 0 0 Control 81324 T1 0.7 0 0 0 T2 2.0 0 0 0 T3 4.2 0 0 0 0 T4 6.5 0 0 0 Last 14.8 0 0 0 Control 90948 T1 0.8 0 0 0 T2 6.1 0 0 0 T3 9.1 0 0 0 T4 16.0 0 0 0 Last 21.5 0 0 0 Control 92568 T1 0.8 0 0 0 T2 5.4 0 0 0 T3 8.7 0 0 0 T4 13.9 0 0 0 ©2019 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-1263/-/DC1 SUPPLEMENTARY DATA Last 17.6 0 0 0 Control 95491 T1 0.9 0 0 0 T2 6.0 0 0 0 T3 8.0 0 0 0 T4/Last 15.0 0 0 0 Control 98695 T1 0.7 0 0 0 T2 5.1 0 0 0 T3 9.4 0 0 0 T4 15.4 0 0 0 Last 22.5 0 0 0 Control 99949 T1 0.8 0 0 0 T2 5.2 0 0 0 T3 8.2 0 0 0 T4 14.1 0 0 0 Last 18.6 0 0 0 AbPos 10929 T1 0.8 0 0 0 0 T2 4.3 0 0 0 0 IA 5.3 1 0 0 0 T3 6.6 1 0 0 0 T4 17.0 1 1 0 Last 23.4 1 1 0 0 AbPos 12712 ©2019 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-1263/-/DC1 SUPPLEMENTARY DATA T1 1.4 0 0 0 T2 3.8 0 0 0 IA 5.8 1 0 0 T3 6.0 1 0 1 T4 6.5 1 0 1 Last 10.0 1 1 1 0 AbPos 15560 T1 0.8 0 0 0 T2 5.0 0 0 0 0 IA 6.0 0 0 1 T3 6.7 0 0 0 1 T4 8.6 1 1 1 Last 14.9 1 1 0 1 AbPos 18895 T1 0.9 0 0 0 T2 5.5 0 0 0 IA 10.1 0 1 0 1 T3 10.2 0 1 0 1 T4 12.0 1 1 0 Last 18.1 0 1 0 1 AbPos 28916 T1 1.3 0 0 0 0 T2 7.3 0 0 0 0 IA 8.3 0 0 0 1 T3 9.3 0 0 0 1 T4 15.2 1 1 0 ©2019 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-1263/-/DC1 SUPPLEMENTARY DATA Last 19.9 0 1 0 1 AbPos 33999 T1 0.7 0 0 0 0 T2 3.1 0 0 0 0 IA 7.9 1 0 1 0 T3 8.1 1 0 1 0 T4 15.7 1 0 0 Last 21.6 1 0 0 0 AbPos 44628 T1 0.8 0 0 0 0 T2 2.0 0 0 0 0 IA 3.0 1 0 1 1 T3 3.1 1 0 1 1 T4 9.1 1 1 1 Last 14.2 1 1 1 1 AbPos 54078 T1 3.5 0 0 0 0 T2 5.5 0 0 0 0 IA 7.4 0 0 0 1 T3 10.3 1 0 0 0 T4 14.1 1 1 0 Last 19.9 1 1 0 0 AbPos 66191 T1 2.1 0 0 0 T2 11.0 0 0 0 0 IA 12.0 1 0 1 0 ©2019 American Diabetes Association.