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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

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Translational cycle of genomic research and clinical application

c cELECTRONIC

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

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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.

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Jefferson Research Data Mart

DEMOGRAPHICSage, ethnicity,

gender, race, vital status

DIAGNOSESICD9/ICD10

CLINICAL LABSLOINC

THERAPYmedications

GENOMIC DATAgene, mutation types, alt allele

frequency, ref dbPROCEDURESICD9/ICD10

BIOREPOSITORIESSNOMED

full pathologic annotation

ONCOLOGY TUMOR DATAprimary disease site, metastases, stage, histology,

outcomes

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Data now available from the Jefferson i2b2 RDM

• Clinical data from hospital clinical data warehouseo Demographics, diagnosis, procedures, labs, medications, hospitalizations,

vitals

• Specimen annotation data from Open Specimeno More than 600,000 specimens from 7 campus biobanko Class, type, pathology

• Tumor registry data from vendor systemo Primary dx, histology, stage, grade, survival, recurrence, treatment, site

specific factors

• Omic data from A/P reports and in-house NGSo Gene, chromosome, mutation type, pathological classification

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Current Jefferson Data Resource Landscape

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

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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

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Drag-and-drop i2b2 query tool

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Taxonomy for biospecimen data

solid, fluid, etc.

frozen, paraffin, etc.malignant, normal

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Taxonomy for tumor registry data

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Taxonomy for NGS data

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Identification of patient cohorts or hypothesis generation

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Additional data on selected cohort can be retieved

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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.

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Case study

Thyroid cancer patients having frozen specimens available for research.

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Example data summaries from the i2b2 RDMCLINICAL DIAGNOSES OF TJUH PATIENTS WITH THYROID SPECIMENS

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Example data summaries from the i2b2 RDMSURVIVAL CURVE (STAGE) OF TJUH PATIENTS WITH THYROID SPECIMENS

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Example data summaries from the i2b2 RDM

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Example data summaries from the i2b2 RDM

DIAGNOSES FOR NRAS AND BRAF POSITIVE CASES