1	Rutgers University Cell and DNA Repository: A Global Resource
2	Genomics Biology (questions) Biotechnology (answers) BIOREPOSITORIES (samples) Convergence
3	What is a Biorepository? Four primary functions of a Biorepository Sample acquisition Processing Storage Distribution
4	Primary RUCDR Functions (expanding services) Receive ~30K blood samples per year Receive samples from individuals and/or nuclear families Produce EBV transformed cell lines as a renewable resource for DNA, RNA, protein and cytogenetic studies Produce 200 (WB) – 1500 µg (LCL) genomic DNA per subject Provide ~150K DNA per year to ~250 labs Single aliquots 96 & 384 well arrays With our partners (i.e., Washington U School of Medicine), provide clinical data for each subject
5	"Speeding discovery of genes for..." Speeding discovery of genes for complex diseases by sharing well annotated, high quality human samples >$15M annual grant & contract support
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7	SOME RUCDR PROJECTS NIDDK Diabetes Type I and Type II (also HBDI) Inflammatory Bowel Disease Kidney and Liver Diseases NIMH Alzheimer Disease Autism (also CAN/AGRE, Simons Simplex Collection) Bipolar Disorder Schizophrenia Pharmacogenetic (clinical) trials NIDA Tobacco Opiates Cocaine Clinical trials NIAAA Alcoholism Longevity/Centenarian (BU/Harvard - Elixir Pharma) Rare Diseases H-G Progeria National Bone Marrow Donor Program Immune Tolerance Network
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11	The RUCDR Role in Research on Populations with Complex Diseases
12	Some Challenges for Genetics Repositories Most DNA are genotyped (e.g., SNPs) soon after collection and provided to several labs who may compare data. Errors are revealed quickly! Samples must be of high quality and uniform concentration Requirement of high throughput assays Must accommodate up to a 5-fold daily variation in number of samples received (labor, space and supplies issues)
13	Sources of errors Sample identity errors are often revealed by lack of Mendelian relationship between samples. Non-paternity, non-maternity (adopted) Mislabeling in field (most common error) Mixing samples from two individuals (especially common when collecting family samples at the same time) Repository errors QA procedures and sample tracking systems allow historic dissection of mislabeling errors (which can then be corrected) Photographing blood tubes/ saving blood sample No manual transcription Capture data on all processing and QA/QC steps
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16	How do you transition a repository? Sample acquisition LIMS Processing Automation Storage Formatting Distribution LIMS / Automation / Formatting
17	New Infrastructure Laboratory Automation Biomek FX Liquid Handlers Tecan Freedom EVO Liquid Handlers QA/QC Caliper LabChip90 Invitrogen Egel System Applied Biosystems 7900HT Enterprise Level LIMS System STARLIMS
18	Technology Development DNA Extraction RNA Extraction Nucleic Acid Distribution Storage System Mycoplasma Testing – Real Time PCR DNA QA/QC – NanoDrop / Invitrogen LIMS Implementation
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20	Operational Requirements I Tracking of samples from pre-registration to receipt to processing to storage to retrieval…with all pertinent sample data linked to each entry Ability to link processing SOPs and QA/QC data to each sample Ability to “select” and “flag” specific samples for operational or quality concerns Ability to “easily” generate reports on all operational components of the biorepository
21	Operational Requirements II Get real time updates on samples being processed Generate pick lists for distributions based on ALL study variables Efficiently manage storage space and run “compression” algorithms to maximize space Integrate essential lab instrumentation and data formats in the LIMS Trigger billing events for services in both grants and contracts
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36	DNA Quality Control / Quality Assurance >500 Samples per Week Labor Intensive Set up Time Intensive HISTORICAL Data Critical for all downstream applications
37	Semi-automated Spectrophotometry Gold Standard
38	Automated DNA Sizing (PCR / Restriction)
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48	Automation Goals
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51	Final Configuration – 48 to 96 Samples
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53	RUCDR