Implementation of Genetic Analysis in Comprehensive Biobank Workflows for Basic Science, Clinical Research and Precision Medicine Applications Dr. Andrew Brooks COO, RUCDR Infinite Biologics Rutgers University www.brookslifesciences.com 1
Planning for the future… We now use biological samples to The future of biosample collection and accomplish important activities to create analysis promises a change in how we think better therapies: about healthcare: - Research and development - Integrative wellness monitoring - Biomarker discovery - Complete health prediction based on genetics and environment - Targeted clinical trials - Whole genome sequencing prior as - Rational drug development early as 6 weeks in pregnancy - Creation of new diagnostics - Comprehensive molecular monitoring for all disease and therapies - Point of care testing…every doctors office, clinic, hospital, and medical center www.brookslifesciences.com 2
Biological Storage/Banking Defined What is the difference between a “Stored” sample and a “Biobank” Sample? A banked sample is proactively acquired for future testing or analysis A banked sample is often sent to multiple different recipients A banked sample should never be depleted www.brookslifesciences.com 3
Repository Management Operations: Enterprise Level Integration www.brookslifesciences.com 4
Adverse Sample Quality Events E XTRACTION C OLLECTION S TORAGE www.brookslifesciences.com 5
Where do the errors come from? Percentage of misidentified samples in a biobank 2% 98% Percentage of collection errors that occur outside of the biobank Dr. Andy Brooks in “Q&A: RUCDR's Andy Brooks on the Challenges Facing Biorepositories and the Rise of Biobank Arrays” BioArray News, April 23, 2013 www.brookslifesciences.com 6
Samples just keep on being collected… what exactly is being analyzed? Sample Collection – No Control Collection errors (98% of biorepository errors) § Variability in sampling and processing § Lack of standardization § Sample Sources – Process Control Fresh Tissue/Blood § Fresh Frozen Tissue/Blood § Formalin Fixed Paraffin Embedded § Cell Lines (lymphoblasts, fibroblasts) § Pluripotent Cells – iPSC’s § www.brookslifesciences.com 7
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 o No manual transcription o Capture data on all processing and QA/QC steps o www.brookslifesciences.com 8
Integrated Processes: Qualification for Downstream Analysis Integrated sample processing, analytical and functional quality control is critical for success on a program wide level www.brookslifesciences.com 9
Identity Theft: Financial vs. Biological Biobanking is the fastest Identity-Theft is the fastest growing component in growing crime in America; 9.9 translational research; over 9 MILLION victims were MILLION samples were reported last year, according collected world wide last to a Federal Trade year, according to a Commission survey! collection of study reports! www.brookslifesciences.com 10
Analytical Quality Control: Moving towards standardization Volume § Contact vs. Non-contact Concentration § Sample heterogeneity Purity/Fidelity § Establishing application dependent metrics Annotation § Critical for comparative analysis Sample Retesting § How often and how to interpret? www.brookslifesciences.com 11
Functional Quality Control: Moving towards standardization DNA § gDNA, WGA, FF DNA RNA § total RNA, mRNA, miRNA Protein § lysates, serum, plasma Tissue § fresh frozen, FFPE, preserved Functional Analysis Over Time www.brookslifesciences.com 12
Nucleic Acid Quality Control Analytical QC Concentration § Purity § Yield § Volume § Functional QC Contamination § Performance § Fingerprint § Subject screening § www.brookslifesciences.com 13
Advances in Functional QC RUID TM QC Panel 96 SNPtype TM Assays Highly polymorphic § Critical performance SNPs § 80% cover Affymetrix and Illumina § Gender, Ethnicity, Parentage § FLEXIBLE § Inexpensive § Integrated Real Time Database Profile comparison § Sample comparison § Gender/Ethnicity calls § Sample performance § LIMS Integration § www.brookslifesciences.com 14
The way we do research and the standard of care is changing 336 Million people in US In 2017 126M hospital visits § 885M doctors office visits § 13B diagnostic tests are with § <10% for molecular analyses Imagine on average 5 biosample aliquots for each person that visited the doctor…4.4B samples Imagine the collection of 5 biomaterials each year for 50 years…220B samples Molecular samples will exceed the number of paraffin blocks by several orders of magnitude www.brookslifesciences.com 15
Science and Technology: Driving Innovation Integrating sample collection, bioprocessing and management with an eye on the molecular central dogma Understanding the power of evolving technologies and developing a sample centric roadmap for future sample use Creation of sample quality control metrics to standardize across all collections Creating a resource that will integrate seamlessly with both industrial and academic collaborative opportunity www.brookslifesciences.com 16
The Promise of Precision Medicine 17
Clinical PGx – Precision Medicine www.brookslifesciences.com 18
Workflow – Current State Sample Sample Sample Collection Processing Distribution & (Clinical Trial) (Biobank) Data Mgmt PGx Data Transfer Genotyping & Analysis (Service Lab) Total Time to Data: ~6-9 mos FTE Allotment: Cost: ~$1750 www.brookslifesciences.com 19
Integrated Biobank & Genetics Workflow OLD NEW www.brookslifesciences.com 20 For Reserarch Use Only – Not for use in diagnostic procedures
Pharmacogenomics Solutions Individual Assays Costly § Incomplete § Subject to validation § Affymetrix DMET Less expansive content § Largely manual process/array development § Affymetrix PharmacoScan Expansive content § Multiple uses for biobank applications § Completely automated § www.brookslifesciences.com 21 For Reserarch Use Only – Not for use in diagnostic procedures
Pharmacogenetics Redefined… Product Application area Highlights Advances in Pharmacogenomics DMET Plus Solution • 1,936 ADME markers in 231 genes • Routine low-volume Available since 2008 • Star allele translation for key genes genotyping • Single sample approach • 4,627 ADME markers in 1,191 genes • Star allele translation for key genes PharmacoScan Solution • Precision PGx profiling • Content from CPIC, PharmaGKB & more Available now • Larger-scale programs • Single-nucleotide polymorphisms (SNPs), • Preemptive screening for healthcare, insertion/deletions (INDELs), copy number variations pharma and biorepositories/biobanks (CNVs) in one run • 24 or 96 batch assay in affordable plate format PharmacoScan Solution DMET Plus Solution For higher-throughput screening For routine use 24- and 96-sample array plate formats Single sample cartridge format www.brookslifesciences.com 22 For Reserarch Use Only – Not for use in diagnostic procedures
Chemistry Principles www.brookslifesciences.com 23 For Reserarch Use Only – Not for use in diagnostic procedures
Fully Automated Workflow www.brookslifesciences.com 24 For Reserarch Use Only – Not for use in diagnostic procedures
Workflow – Ideal State Biobank Integration Sample Sample Sample Processing & PGx Collection Storage Genotyping (Clinical Trial) (Biorepository) (Service Lab) Data Transfer & Analysis (GWAS, HLA, DMET, etc…) Total Time to Data: Real-time FTE Allotment: Cost: ~$200 www.brookslifesciences.com 25
Advantages of Biobank & Genetic Analysis Integration • Data Quality – Process combined with functional QC – Enhanced subject stratification – Critical information for drug/therapy development • Types of Data – Integrate “screening” with “deep analysis” • Time to Data – Reduced by months and allows for rapid analysis real time or immediately following consent review • Fiscal Advantages – Up to 50% reduction in operating costs www.brookslifesciences.com 26
Past, Recent Past, Present Past Recent Past + Present + • 4 www.brookslifesciences.com 27
Overall Advantages of Biobanking & PGx Genetic Analysis Integration Data Quality Process combined with functional QC § Critical information for drug development and subject stratification § Time to Data Reduced by months which also leads to additional cost reductions § Fiscal Advantages Up to 50% reduction in operating costs § www.brookslifesciences.com 28
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