Individualized Health Background Method Application Summary Estimating AutoAntibody Signatures to Detect Autoimmune Disease Patient Subsets Zhenke Wu Assistant Professor Department of Biostatistics, University of Michigan 27 July 2017 The 62nd Annual International Biometric Society Meeting of the Brazilian Region (RBras 2017) R package: spotgear https://github.com/zhenkewu/spotgear Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 1 / 30
Individualized Health Background Method Application Summary Common Questions on Individual and Population Health 1. a. What is the person’s health state given health measurements? b. What is the population distribution of health states? (Wu et al., 2015, JRSS-C ; Wu and Zeger, 2016a,b) 2. a. What is the person’s health trajectory? b. What is the population’s characteristics of health trajectory? 3. Does a particular intervention improve health - on average/for a particular person? (Wu et al., 2014, Biometrics ; Frangakis, Qian, Wu, Diaz, 2015, Biometrics ) 4. Are interventions being used optimally? Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 2 / 30
Individualized Health Background Method Application Summary Example I Pneumonia Etiology Research for Child Health (PERCH) Background: • > 30 possible infectious causes • Difficult to directly observe Goal: • Population disease etiology estimation • Individual diagnosis Study details: • $40-mil, Gates-funded 7-country study; Sites at Sub-Saharan Africa and South Asia • Diverse measures; variable precisions • ∼ 5,000 cases and ∼ 5,000 controls Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 3 / 30
Individualized Health Background Method Application Summary Measurements of Different Quality Measurement Latent Health State Measurements Precisions 𝑇 𝐽 𝑀 (𝜄, 𝜔) 𝑁 𝑗 𝑗 cases controls Specimen (S) (~5,000) (~5,000) Nasopharyngeal Bronze- PCR Standard (BrS) Blood Culture NA Silver- Standard (SS) Lung Infection Lung aspirate NA NA Gold- Standard (GS) -------- *NP: nasopharyngeal; PCR: polymerase chain reaction; LA: lung aspirate Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 4 / 30
Individualized Health Background Method Application Summary Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 5 / 30
Individualized Health Background Method Application Summary Example II: Raw Data Gel Electrophoresis Autoradiography; 20 Samples Raw Image Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 6 / 30
Individualized Health Background Method Application Summary Example II: Raw Data Gel Electrophoresis Autoradiography; 20 Samples Raw Image Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 6 / 30
Individualized Health Background Method Application Summary Example II: Raw Data Gel Electrophoresis Autoradiography; 20 Samples Raw Image Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 6 / 30
Individualized Health Background Method Application Summary Example II: Raw Data Gel Electrophoresis Autoradiography; 20 Samples Raw Image Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 6 / 30
Individualized Health Background Method Application Summary Example II: Raw Data Gel Electrophoresis Autoradiography; 20 Samples Raw Image Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 6 / 30
Individualized Health Background Method Application Summary Example II: Raw Data Gel Electrophoresis Autoradiography; 20 Samples Raw Image Hand-picked Bands “ | ” Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 6 / 30
Individualized Health Background Method Application Summary Roadmap Laboratory Data (AutoAntibody Profile) Add cell lysate Visualize the IP (contain proteins that bands AutoAntibodies bind, (Autoradiography) e.g., Ro60, RNP , PL-7 and centromere) Obtain a mixture of Enroll Separate Obtain binded AutoAntibodies by Autoimmune Serum Samples AutoAntibodies, Gel Electrophoresis Disease (contain i.e. Immuno- (SDS-PAGE gels) Patients AutoAntibodies) Precipitation (IP) Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 7 / 30
Individualized Health Background Method Application Summary Roadmap Data Science (Patient Subsetting) Patient Subsetting with distinct AutoAntibody Signatures Laboratory Data (AutoAntibody Profile) Add cell lysate Add cell lysate Visualize the IP Visualize the IP (contain proteins that (contain proteins that bands bands AutoAntibodies bind, AutoAntibodies bind, (Autoradiography) (Autoradiography) e.g., Ro60, RNP e.g., Ro60, RNP , , PL-7 and PL-7 and centromere) centromere) Obtain a mixture of Obtain a mixture of Enroll Enroll Separate Separate Obtain Obtain binded binded AutoAntibodies by AutoAntibodies by Autoimmune Autoimmune Serum Samples Serum Samples AutoAntibodies, AutoAntibodies, Gel Electrophoresis Gel Electrophoresis Disease Disease (contain (contain i.e. Immuno- i.e. Immuno- (SDS-PAGE gels) (SDS-PAGE gels) Patients Patients AutoAntibodies) AutoAntibodies) Precipitation (IP) Precipitation (IP) Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 7 / 30
Individualized Health Background Method Application Summary Roadmap Data Science (Patient Subsetting) Patient Subsetting with distinct AutoAntibody Signatures Laboratory Data (AutoAntibody Profile) Phenotypic Data Add cell lysate Add cell lysate Visualize the IP Visualize the IP (contain proteins that (contain proteins that bands bands AutoAntibodies bind, AutoAntibodies bind, 1) Johns Hopkins Autoimmune Disease (Autoradiography) (Autoradiography) e.g., Ro60, RNP e.g., Ro60, RNP , , Patient Cohort with phenotype data PL-7 and PL-7 and centromere) centromere) (cancer type, organ functions, etc.) 2) Population Cancer Registry Data as Obtain a mixture of Obtain a mixture of Enroll Enroll Separate Separate Obtain Obtain reference (Surveillance, Epidemiology binded binded AutoAntibodies by AutoAntibodies by Autoimmune Autoimmune Serum Samples Serum Samples AutoAntibodies, AutoAntibodies, and End Results - SEER) Gel Electrophoresis Gel Electrophoresis Disease Disease (contain (contain i.e. Immuno- i.e. Immuno- (SDS-PAGE gels) (SDS-PAGE gels) Patients Patients AutoAntibodies) AutoAntibodies) Precipitation (IP) Precipitation (IP) Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 7 / 30
Individualized Health Background Method Application Summary Roadmap Data Science (Patient Subsetting) Risk stratification (with cancer phenotypes) Patient Predict the magnitude & timing Subsetting of cancer risks in each subset, with distinct e.g., AutoAntibody “Which AutoAntibody Signatures signatures protect an individual against cancer?“ Laboratory Data (AutoAntibody Profile) Phenotypic Data Add cell lysate Add cell lysate Visualize the IP Visualize the IP (contain proteins that (contain proteins that bands bands AutoAntibodies bind, AutoAntibodies bind, 1) Johns Hopkins Autoimmune Disease (Autoradiography) (Autoradiography) e.g., Ro60, RNP e.g., Ro60, RNP , , Patient Cohort with phenotype data PL-7 and PL-7 and centromere) centromere) (cancer type, organ functions, etc.) 2) Population Cancer Registry Data as Obtain a mixture of Obtain a mixture of Enroll Enroll Separate Separate Obtain Obtain reference (Surveillance, Epidemiology binded binded AutoAntibodies by AutoAntibodies by Autoimmune Autoimmune Serum Samples Serum Samples AutoAntibodies, AutoAntibodies, and End Results - SEER) Gel Electrophoresis Gel Electrophoresis Disease Disease (contain (contain i.e. Immuno- i.e. Immuno- (SDS-PAGE gels) (SDS-PAGE gels) Patients Patients AutoAntibodies) AutoAntibodies) Precipitation (IP) Precipitation (IP) Zhenke Wu( zhenkewu@umich.edu ) RBras62, UFLA, Lavras, MG, Brazil 27 July 2017 7 / 30
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