Vanderbilt’s DNA Databank
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Vanderbilt’s DNA Databank : BioVU. Personalized Medicine. Integration of genomic information into clinical decision making Personalized disease treatment and also preventative therapies. Personalized Medicine.

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Vanderbilt’s DNA Databank : BioVU

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Vanderbilt s dna databank biovu

Vanderbilt’s DNA Databank:

BioVU


Personalized medicine

Personalized Medicine

  • Integration of genomic information into clinical decision making

  • Personalized disease treatment and also preventative therapies


Personalized medicine1

Personalized Medicine

  • A SNP is a single base-pair mutation that occurs at a specific site in the DNA sequence - occurs in at least 1% of the population

  • SNPs are responsible for over 80% of the variation between two individuals; they are ideal for establishing correlations between genotype and phenotype

  • As some SNPs predispose individuals to have a certain disease or trait or react to a drug in a different way, they will be highly useful in diagnostics and drug development


What is biovu

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

  • Current sample number: 116,551

    • 105,910adult samples

    • 10,641pediatric samples


Vanderbilt s dna databank biovu

Extract DNA

John Doe

A7CCF99DE65732….

eligible

A7CCF99DE5732….

One way hash

scrubbed

A7CCF99DE65732….

John Doe

The “synthetic derivative”

(SD): can be updated


Vanderbilt s dna databank biovu

Synthetic Derivative vs. BioVU

A7CDE6532….

+

scrubbed

scrubbed

A7CDE6532 ….

A7CDE6532 ….

Synthetic Derivative BioVU

~1.9 million ~116,000


The synthetic derivative

The Synthetic Derivative

  • A Derivative of the EMR - information content reduced by ‘scrubbing’ identifiers

  • Systematically shifted event dates

  • Contains ~1.9 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 9/31/09

  • Can be searched restricting to records for which DNA is available


Vanderbilt s dna databank biovu

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)


Vanderbilt s dna databank biovu

BioVU Program Review


Sample accrual

Sample accrual


Vanderbilt s dna databank biovu

BioVU Sample Management

RTS SmaRTStore


Validation in biovu

Validation in BioVU

  • Sample handling algorithms

    • Gender match

    • 1/384 gender mismatches

  • Ancestry

    • Characterize sample ancestry, assess usefulness of ‘race’ as defined in EMR

    • Provide a panel of ancestry informative markers that define ancestry

    • No significant difference between the concordance of self-report or observer-report with genetic ancestry

  • Demonstration project – American Journal of Human Genetics

    • Can known associations between genetic variants and common diseases be identified in the EMR?


The demonstration project

The “demonstration project”

Genotype “high-value” SNPs in the first 8,000 samples accrued.

including SNPs associated by replicated genome-wide experiments with common diseases & traits

Atrial fibrillation

Crohn’s disease

Multiple Sclerosis

Rheumatoid arthritis

Type II Diabetes

Develop Natural Language Processing methods to identify cases and controls

Are genotype-phenotype relations replicated?


First results

First results

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


Vanderbilt s dna databank biovu

First results

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


Types of projects

Types of projects

  • Discovery or validation of genotype-phenotype relations for disease susceptibility or drug responses

  • Discovery of new disease/susceptibility genes  resequence in patients (obesity, Cushing's, susceptibility to infection, insomnia, pre-term birth)

  • Access samples without disease X, or “normals” of specified ancestry, or old normals

  • Phenome-wide association study (PheWAS): in development


Research use cases

Retrospective chart reviews

Hypothesis

generation

Rapid preliminary

data for

grant

submissions

Feasibility assessment

Research Use Cases


Vanderbilt s dna databank biovu

Examples of ICD-9 codes

for rare diseases


Vanderbilt s dna databank biovu

cases

controls

Investigator query

Data use agreement + IRB Approval

+


Vanderbilt s dna databank biovu

cases

controls

Investigator query

Data use agreement + IRB Approval

Manual Review

+


Vanderbilt s dna databank biovu

cases

cases

controls

controls

+

Investigator query

Data use agreement + IRB Approval

Sample retrieval

+


Vanderbilt s dna databank biovu

cases

cases

controls

controls

+

Genotyping, genotype-phenotype relations

Investigator query

Data use agreement + IRB Approval

Sample retrieval

+


Data use agreement

Data Use Agreement


Genotyping data accrual

Genotyping Data Accrual


Vanderbilt s dna databank biovu

Nationally Prevalent Diseases in the African American Population


Vanderbilt s dna databank biovu

BioVU Application Process

Proposal Review Process:

Investigator(s) completes

BioVU Application Process

Investigator(s) completes

VICTR Resource Request

Proposal reviewed by

BioVU Review Committee

BioVU program office contacts

investigators with any necessary

revisions if applicable

Funding request reviewed

by VICTR SRC

Investigator resubmits

proposal if necessary

Funding Decision

Proposal Approved/

Access granted

Total Time:

Data Requests: 4-6 weeks

DNA Access: 8-12 weeks


Vanderbilt s dna databank biovu

BioVU Genotyping Process

BioVU Genotyping Process:

Investigator selects cases

and controls from

Synthetic Derivative

Genotyped data analyzed

by investigator

Investigator signals BioVU program

to initiate sample selection

Investigator and BioVU program

receive genotype data

BioVU notifies DNA resources core

that samples are ready for

selection and picking

Samples are provided to

appropriate lab and are genotyped


Biovu requests

BioVU Requests

37 Total Requests

24 Approvals


Faq answers

FAQ “answers”

  • SD access: “non-human subjects” IRB review (days)

  • Current access costs: $4/sample

  • Genotyping:

    • Investigator-funded

      • Consider VICTR as a funding source

    • Genotyping/sequencing performed in VUMC Core Facilities

      • Justification must be provided for outside genotyping, including quality control plans

    • Genotype “redeposit” part of the data use agreement

  • Anticipate 16,000 BioVU subjects will have GWAS-type genotyping data by fall 2011


Vanderbilt s dna databank biovu

Questions?

Contact: Erica Bowton PhD

BioVU Program Manager

[email protected]

322-1975


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