1. 1 Jack London, PhD Research Professor, Cancer Biology Thomas Jefferson University Informatics Shared Resource Director Sidney Kimmel Cancer Center at Jefferson OpenSpecimen Meeting December 9, 2014 Integrating OpenSpecimen data in i2b2 research data marts

2. 2 Translational cycle of genomic research and clinical application cc ELECTRONIC MEDICAL RECORD Diagnoses, treatments, and outcomes MOLECULAR DIAGNOSTIC LAB RESULTS Clinically actionable reports BASIC SCIENCE RESEARCH Discovery of clinically significant biomarkers RESEARCH DATA MART BIOREPOSITORIES HOSPITALUNIVERSITY CLINICAL DATA WAREHOUSE

3. 3 Jefferson i2b2 Research Data Mart Built on “informatics for integrating biology and the bedside” (i2b2) framework from the NIH-funded National Center for Biomedical Computing based at Partners HealthCare System (Harvard). RDM data are de-identified. Re-identification possible via an honest broker, who has access to a re-identification application. Currently > 40 million observations on > 400,000 patients. Data refreshed weekly.

4. 4 Jefferson Research Data Mart DEMOGRAPHICS age, ethnicity, gender, race, vital status DIAGNOSES ICD9/ICD10 CLINICAL LABS LOINC THERAPY medications GENOMIC DATA gene, mutation types, alt allele frequency, ref db PROCEDURES ICD9/ICD10 BIOREPOSITORIES SNOMED full pathologic annotation ONCOLOGY TUMOR DATA primary disease site, metastases, stage, histology, outcomes

5. 5 Data now available from the Jefferson i2b2 RDM Clinical data from hospital clinical data warehouse o Demographics, diagnosis, procedures, labs, medications, hospitalizations, vitals Specimen annotation data from Open Specimen o More than 600,000 specimens from 7 campus biobank o Class, type, pathology Tumor registry data from vendor system o Primary dx, histology, stage, grade, survival, recurrence, treatment, site specific factors Omic data from A/P reports and in-house NGS o Gene, chromosome, mutation type, pathological classification

6. 6 Current Jefferson Data Resource Landscape

7. 7 Cancer researchers often wish to link tumor registry annotation with available specimens

8. 8 Genomic annotation details ABL1 APC ATM BRAF CSF1R ERBB4 FBXW7 FGFR2 FGFR3 FLT3 G11 GQ HNF1A HRAS IDH1 JAK3 KDR KRAS MET MPL NOTCH1 NPM1 NRAS PDGFRA PIK3CA PTEN RB1 RET SMAD4 SMO SRC STK11 TP53 VHL GENES Patient genomic annotation includes: gene mutation result (POSITIVE or NEGATIVE) alternate allele frequency mutation type nucleotide change protein change COSMIC ID DBSNP ID

9. 9 Drag-and-drop i2b2 query tool

10. 10 Taxonomy for biospecimen data solid, fluid, etc. frozen, paraffin, etc. malignant, normal

11. 11 Taxonomy for tumor registry data

12. 12 Taxonomy for NGS data

13. 13 Identification of patient cohorts or hypothesis generation

14. 14 Additional data on selected cohort can be retieved

15. 15 Current uses of Jefferson’s Research Data Mart i2b2 query interface is the primary access portal for identifying biospecimens available for research. The RDM provides cohort size estimates for prospective studies grant applications, and is used in the design phase of clinical trials to estimate of recent patient population satisfying proposed eligibility rules. The RDM provides comprehensive patient annotation for ongoing research projects. And, in support of Personalized Medicine, the RDM is used in Next Generation Sequencing (NGS) studies to discover cancer biomarkers for targeted treatment of individual patients.

16. 16 Case study Thyroid cancer patients having frozen specimens available for research.

17. 17 Example data summaries from the i2b2 RDM CLINICAL DIAGNOSES OF TJUH PATIENTS WITH THYROID SPECIMENS

18. 18 Example data summaries from the i2b2 RDM SURVIVAL CURVE (STAGE) OF TJUH PATIENTS WITH THYROID SPECIMENS

19. 19 Example data summaries from the i2b2 RDM

20. 20 Example data summaries from the i2b2 RDM DIAGNOSES FOR NRAS AND BRAF POSITIVE CASES