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Automating a biorepository program: Rutgers University Cell and DNA Repository (RUCDR) Case Study

Automating a biorepository program: Rutgers University Cell and DNA Repository (RUCDR) Case Study. Dr. Andrew Brooks Associate Professor of Genetics COO, Rutgers University Cell and DNA Repository Director, Bionomics Research and Technology Center

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Automating a biorepository program: Rutgers University Cell and DNA Repository (RUCDR) Case Study

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  1. Automating a biorepository program: Rutgers University Cell and DNA Repository (RUCDR) Case Study Dr. Andrew Brooks Associate Professor of Genetics COO, Rutgers University Cell and DNA Repository Director, Bionomics Research and Technology Center Environmental and Occupational Health Science Institute Human Genetics Institute of New Jersey Rutgers University

  2. Speeding discovery of genes for complex diseases by sharing well annotated, high quality human samples >$30M annual grant & contract support Mission RUCDR enables sharing programs (DNA, RNA, cell lines, tissue and clinical data) for NIH Institutes, research advocacy groups & biotechnology corporations • >100 Technical Staff • 35,000 sq. ft. laboratory and storage space • 6M nucleic acid samples & 4.5M cell lines • Distribute ~ 1M samples for discovery based research

  3. SELECTED 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) • Bipolar Disorder • Schizophrenia • Pharmacogenetic (clinical) trials • NIDA • Tobacco • Opiates • Cocaine • Clinical trials • NIAAA / COGA • Alcoholism • Simons Simplex Collection • Autism • Immune Tolerance Network

  4. 5 Major Program Functions:Seamless integration/automation • Sample acquisition • Processing • Storage • Distribution • Analysis

  5. Functional Essentials:Maximizing Biological Resources • Maximal use of primary samples • Undefined application for downstream analyses • Efficient processing • Maximizing extraction technologies to improve yield and quality • Appropriate storage • Defining storage formats and temperatures to maximize storage infrastructure • Nucleic acid amplification / Cell line establishment • Creating renewable resources to preserve primary sample and/or precious collections • Appropriate distribution guidelines • Define needs for specific downstream applications to preserve sample resources

  6. Application “Independent” Workflows • Sample Pre-Registration • Hundreds of sites globally • Sample Accessioning • Scalable and qualitative • Sample Validation • Process initiation • Processing / QC • Analytical and Functional Measurements • Sample Storage • Variable temperatures and formats • Sample Distribution • Custom requests and sample management

  7. Processing Statistics (yearly) • >200,000 Nucleic Acid Extractions • DNA from WB • DNA from CP • DNA from plasma/serum/tissue • RNA from blood • RNA from tissue • >5M QPCR reactions • Standard QPCR • HT screening (36M rxns) • >10,000 DNA Microarrays • SNP genotyping • Gene expression Automation of key components is essential

  8. RUCDR Automation Infrastructure • 10 Liquid Handlers (Open Systems) • Multiple technologies • No dedicated applications • 9 Application Specific Systems • Defined sample processing • Limited flexibility • 6 Tube Handling Systems • Commensurate with manual storage • 20+ Analytical Instruments • Quality control • High throughput screening • Discovery

  9. Building infrastructure… • How do we transition an established protocol to an automated process? • How do we transition established storage formats to an automated solution…long on human resources? • Next phase for RUCDR • What do you want your program to be when it grows up? “Do we ever have to grow up”…Peter Pan • Leveraging existing technology infrastructure and expertise to weather the transitional process

  10. Technology Evaluation Best Practices… • Deciding on open source vs. closed platforms • Application specific solutions • Often small changes can have a large deferred impact on your ability to expand service offerings • What to expect from vendors once the sale is over • Protect your application investment • What do you do with “historical” data after making a technology change? • Don’t assume that a change you make is suitable for everyone you serve • How many technology changes can your program withstand over a short period of time • Make fewer strategic changes for healthy growth

  11. Cost considerations:Automation acquisition • Acquisition of technology • Staffing of technology • Sample/reagents • Yearly maintenance • Opportunity costs • Cost of being “first” • Cost of being “last”

  12. To Automate or not to Automate:That is the operational question… • TO Automate • Build an open infrastructure • Every automated protocol needs a manual counterpart • Automation does not replace technicians • Keep feeding your liquid handlers for best performance • NOT TO Automate • Integrated processes that tie up lab infrastructure • Low throughput procedures • Protocols with extensive variables *Automation is essential for high volume lab services

  13. Workflow Analysis Sample DNA/RNA Extraction Nucleic Acid Amplification Sample Archival Sample Distribution Qualitative & Quantitative Analyses Comprehensive Tracking

  14. DNA QC Workflow Evolution OLD NEW Gender Polymorphic

  15. RNA Extraction Workflows Analytical QC Extraction >800/day cDNA Amplification QPCR Vendor & Technology Agnostic Arrays Functional QC NextGen

  16. DNA Quality Control • Analytical QC • Concentration • Purity • Yield • Volume • Functional QC • Contamination • Performance • Fingerprint • Subject screening Static Biostorage Dynamic Discovery

  17. RUIDTM QC Panel • 96 SNPs • Highly polymorphic • 80% cover Affymetrix and Illumina • Gender • Ethnicity • FLEXIBLE • Inexpensive • Integrated Real Time Database • Profile comparison • Sample comparison • Gender/Ethnicity calls • Sample performance • LIMS Integration

  18. RUCDR IDTM Data Resource • Millions of data points collected • 10K+ samples/month • Rapidly determine sample contamination/processing errors • Proactively address sample registration errors • Catalogue all RUCDR DNA samples continuously RUCDR DNA QC Database

  19. DNA/RNA Analysis:Downstream Applications • Non-QPCR • Microarrays • NextGen Sequencing • QPCR/QFPCR • Research applications • Diagnostic applications • High Throughput Technologies Flexibility is ESSENTIAL Sensitivity is CRITICAL Quantitation is CRITICAL

  20. Workflows, Workflows, Workflows…

  21. Project Level Control

  22. Defined Access = + Outside User Access Technician Access Manager Access

  23. “Forcing” Harmonization How do you get… Hundreds of Sites to register… Tens of Services which creates… Thousands of biologicals which are sent to… Hundreds of Investigators for… Global Studies without… Losing your samples or your mind!

  24. Biobanking: A constant state of transition… • All samples are limiting and precious • Having comparable data is essential • Integrated Sample Quality Control “Keep eating… we will make more” “Keep collecting… we will process more”

  25. Come visit us…Lunch Time Tours!! Applying Technological & Business Infrastructure to Complex Disease Research http://www.RUCDR.org brooks@biology.rutgers.edu

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