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BioVU and the Synthetic Derivative Erica Bowton, PhD Program Manager, Personalized Medicine

BioVU and the Synthetic Derivative Erica Bowton, PhD Program Manager, Personalized Medicine. Personalized Medicine. What is BioVU ?. The move towards personalized medicine requires very large sample sets for discovery and validation

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BioVU and the Synthetic Derivative Erica Bowton, PhD Program Manager, Personalized Medicine

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  1. BioVU and the Synthetic Derivative Erica Bowton, PhD Program Manager, Personalized Medicine

  2. Personalized Medicine

  3. What is BioVU? The move towards personalized medicine requires very large sample sets for discovery and validation BioVU: biobank intended to support a broad view of biology and enable personalized medicine Contains de-identified DNA extracted from leftover blood after clinically-indicated testing of Vanderbilt patients who have not opted out Linked to Synthetic Derivative: de-identified EMR

  4. John Doe

  5. One way hash scrubbed A7CCF99DE65732…. John Doe ~2 million records The Synthetic Derivative: can be updated

  6. Extract DNA John Doe A7CCF99DE65732…. eligible A7CCF99DE5732…. One way hash scrubbed A7CCF99DE65732…. John Doe ~2 million records The Synthetic Derivative: can be updated

  7. How BioVU Samples are Accepted • Accepted samples must: • Be of good quality • Have sufficient amount of blood • Be from a patient who has signed the BioVU form • Be from a patient who has not opted out

  8. The BioVU FormA component of the Consent for Treatment process

  9. Awareness Generation • Posters in phlebotomy areas in English and Spanish • Brochures freely available to VUMC clinics in English and Spanish • BioVU hotline available for questions and opt-out

  10. Current accrual as of 2-19-2014: 155,090 adult 21,472 pediatric • BioVU Sample Accrual: 176,448

  11. Where are BioVU samples stored? RTS SmaRTStore

  12. BioVU Operations Oversight Institutional Review Board = oversight = input, advisory BioVU Ethics Advisory Board* BioVU Protocol Review Committee General Counsel Med Ctr Ethics Community Advisory Board* Vice Chancellor’s Office Operations Oversight Board** Vice Chancellor (Chair) Clin. Pharmacology(PI) Ethics/ELSI (2) Patient advocacy (2) Ctr Human Genetics Research (2) University counsel (1) Clinical genetic testing lab (1) Biostatistics (3) Genetics/Genetic Medicine (6) Cancer center (3) Pediatric genetics (1) * Includes (or exclusively) external membership ** (n)= number of members representing this discipline/area. Several members are represented in more than one area Program staff

  13. Resources for EMR-based research at VUMC The Synthetic Derivative A de-identified and continuously-updated image of the EMR (2 M records) • BioVU • DNA samples available: >175,000 • Plasma collection underway • Redeposited genotypes • Subjects with GWAS data: >12,000 • Subjects with any genotyping: >60,000 • > 8,000,000,000 genotypes 13

  14. The Synthetic Derivative • Rich, multi-source database of de-identified clinical and demographic data • A Derivative of the EMR - information content reduced by ‘scrubbing’ identifiers • Systematically shifted event dates • User Interface tool that can be used for access and analysis • Services are available to help deliver results for non-standard queries (temporal queries, controls matching, etc) • Contains ~2.1 million records • ~1 million with detailed longitudinal data • averaging 100,000 bytes in size • an average of 27 codes per record • Records updated over time and are current through 8/31/13

  15. Synthetic Derivative Data Types • Narratives, such as: • Clinical Notes • Discharge Summaries • History and Physicals • Problem Lists • Surgical Reports • Progress Notes • Letters • Diagnostic Codes, Procedural Codes • Forms (intake, assessment) • Reports (pathology, ECGs, echocardiograms) • Clinical Communications • Lab Values and Vital Signs • Medication Orders • TraceMaster (ECGs) • Tumor Registry

  16. Technology + policy • De-identification • Derivation of 128-character identifier (RUI) from the MRN generated by Secure Hash Algorithm (SHA-512) • HIPAA identifiers removed using combination of custom techniques and established de-identification software • Date Shift • Our algorithm shifts the dates within a record by a time period (up to 364 days backwards)that is consistent within each record, but differs across records • Restricted access & continuous oversight • Access restricted to VU; not a public resource • IRB approval for study (non-human) • Data Use Agreement • Audit logs of all searches and data exports

  17. Data Use Agreement • No attempt at re-identification • Inform BioVU staff if a record is identifiable • Research confined to that which is described • Genotypes to be re-deposited back to BioVU

  18. Phenotyping Approach Algorithm Development <95% Case & control algorithm development and refinement Identify phenotype of interest Manual review; assess precision ≥95% Deploy in BioVU

  19. Disease Cohorts

  20. BioVU Utilization • Pre-Review • BioVU Committee Review • Expedited Review • Genotyping data requests • Reviewed by BioVU Chair • Full Review • DNA sample access requests • Reviewed and scored by Primary and Secondary reviewers • BioVU Projects: • Requests: 104 • Approved so far: 86

  21. Current BioVU Studies

  22. USE CASE 1Synthetic Derivative Study

  23. USE CASE 1Synthetic Derivative Study BMI Normal Range Zyprexa Prescription Ability to analyze quantitative, longitudinal repeated measures

  24. USE CASE 1Synthetic Derivative Study

  25. USE CASE 1Synthetic Derivative Study

  26. USE CASE 1Synthetic Derivative Study

  27. USE CASE 1Synthetic Derivative Study 0 13.3 26.2 40.9 73.4 300+ BMI

  28. USE CASE 2Existing Genetic Data

  29. USE CASE 2Existing Genetic Data

  30. USE CASE 2Existing Genetic Data

  31. USE CASE 2Existing Genetic Data

  32. USE CASE 2Existing Genetic Data

  33. USE CASE 2Existing Genetic Data

  34. USE CASE 3New Genotyping/Sequencing

  35. USE CASE 3New Genotyping/Sequencing

  36. USE CASE 3New Genotyping/Sequencing

  37. USE CASE 3New Genotyping/Sequencing

  38. USE CASE 3New Genotyping/Sequencing Investigator query Data use agreement One way hash cases + controls

  39. Investigator query Data use agreement One way hash Data analysis cases + controls

  40. cases + Genotyping, genotype-phenotype relations Investigator query controls Data use agreement One way hash Sample retrieval cases + controls

  41. BioVU Project Life Cycle • Access approvals/application • Cohort identification • Clinical data extraction • Programming support • Study design • Agreements • Genomic data analysis and research design • Biostatistical/bioinformatic support 1-2 months 2-3 months 1-2 months • Genotyping/sequencing approaches • Assay design • SNP selection • Sample pulling and plating

  42. For ALL BioVU Studies… Resources: 1. BioVU Project Management: BioVU@vanderbilt.edu 2. Programming services: IDASC CORE 3. Genomic technologies: VANTAGE CORE 4. Data analysis services: VANGARD CORE https://starbrite.vanderbilt.edu/biovu/

  43. END

  44. Validating EMR phenotype algorithms published observed gene / disease marker region rs2200733 Chr. 4q25 Atrial fibrillation rs10033464 Chr. 4q25 rs11805303 IL23R rs17234657 Chr. 5 Crohn's disease rs1000113 Chr. 5 rs17221417 NOD2 rs2542151 PTPN22 rs3135388 DRB1*1501 Multiple sclerosis rs2104286 IL2RA rs6897932 IL7RA rs6457617 Chr. 6 Rheumatoid arthritis rs6679677 RSBN1 rs2476601 PTPN22 rs4506565 TCF7L2 rs12255372 TCF7L2 rs12243326 TCF7L2 rs10811661 CDKN2B Type 2 diabetes rs8050136 FTO rs5219 KCNJ11 rs5215 KCNJ11 rs4402960 IGF2BP2 0.5 1.0 5.0 2.0 Odds Ratio Ritchie et al, 2010

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