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Implementation of Genetic Analysis in Comprehensive Biobank Workflows for Basic Science, Clinical Research and Precision Medicine ApplicationsDr. Andrew BrooksCOO, RUCDR Infinite BiologicsRutgers University
www.brookslifesciences.com 2
We now use biological samples to accomplish important activities to create better therapies:- Research and development- Biomarker discovery- Targeted clinical trials- Rational drug development- Creation of new diagnostics
The future of biosample collection and analysis promises a change in how we think about healthcare:- Integrative wellness monitoring- Complete health prediction based on
genetics and environment- Whole genome sequencing prior as
early as 6 weeks in pregnancy- Comprehensive molecular monitoring
for all disease and therapies- Point of care testing…every doctors
office, clinic, hospital, and medical center
Planning for the future…
A banked sample is proactively acquired for future testing or analysisA banked sample is often sent to multiple different recipientsA banked sample should never be depleted
What is the difference between a “Stored” sample and a “Biobank” Sample?
Biological Storage/Banking Defined
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Where do the errors come from?
2%98%
Percentage of misidentified samples in a biobank
Percentage of collection errors that occur outside of the biobank
Dr.AndyBrooksin“Q&A:RUCDR'sAndyBrooksontheChallengesFacingBiorepositoriesandtheRiseofBiobankArrays”BioArrayNews,April23,2013
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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
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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)
o Photographing blood tubes/ saving blood sample
o No manual transcription
o Capture data on all processing and QA/QC stepswww.brookslifesciences.com 8
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Integrated sample processing, analytical and functional quality control is critical for success on a program wide level
IntegratedProcesses:QualificationforDownstreamAnalysis
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Identity Theft: Financial vs. Biological
Identity-Theft is the fastest growing crime in America; 9.9 MILLION victims were reported last year, according to a Federal Trade Commission survey!
Biobanking is the fastest growing component in translational research; over 9 MILLION samples were collected world wide last year, according to a collection of study reports!
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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?
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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 Timewww.brookslifesciences.com 12
Nucleic Acid Quality Control
Analytical QC§ Concentration§ Purity§ Yield§ Volume
Functional QC§ Contamination§ Performance§ Fingerprint§ Subject screening
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Advances in Functional QCRUIDTM QC Panel
96 SNPtypeTM 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
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The way we do research and the standard of care is changing
336 Million people in USIn 2017§ 126M hospital visits§ 885M doctors office visits§ 13B diagnostic tests are with
<10% for molecular analysesImagine on average 5 biosamplealiquots for each person that visited the doctor…4.4B samplesImagine the collection of 5 biomaterials each year for 50 years…220B samplesMolecular samples will exceed the number of paraffin blocks by several orders of magnitude
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Science and Technology: Driving Innovation
Integrating sample collection, bioprocessing and management with an eye on the molecular central dogmaUnderstanding the power of evolving technologies and developing a sample centric roadmap for future sample useCreation of sample quality control metrics to standardize across all collectionsCreating a resource that will integrate seamlessly with both industrial and academic collaborative opportunity
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Sample Collection
(Clinical Trial)
Sample Processing(Biobank)
Sample Distribution &
Data Mgmt
PGxGenotyping
(Service Lab)
Data Transfer & Analysis
Total Time to Data: ~6-9 mosFTE Allotment: Cost: ~$1750
Workflow – Current State
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OLD
NEW
Integrated Biobank & Genetics Workflow
For Reserarch Use Only – Not for use in diagnostic procedureswww.brookslifesciences.com 20
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
For Reserarch Use Only – Not for use in diagnostic procedureswww.brookslifesciences.com 21
Advances in PharmacogenomicsProduct Application area Highlights
DMET Plus SolutionAvailable since 2008 • Routine low-volume
genotyping
• 1,936 ADME markers in 231 genes• Star allele translation for key genes• Single sample approach
PharmacoScan SolutionAvailable now
• Precision PGx profiling• Larger-scale programs• Preemptive screening for healthcare,
pharma and biorepositories/biobanks
• 4,627 ADME markers in 1,191 genes• Star allele translation for key genes• Content from CPIC, PharmaGKB & more• Single-nucleotide polymorphisms (SNPs),
insertion/deletions (INDELs), copy number variations (CNVs) in one run
• 24 or 96 batch assay in affordable plate format
DMET Plus Solution PharmacoScan SolutionFor routine use For higher-throughput screening
24- and 96-sample array plate formatsSingle sample cartridge format
Pharmacogenetics Redefined…
For Reserarch Use Only – Not for use in diagnostic procedureswww.brookslifesciences.com 22
Chemistry Principles
For Reserarch Use Only – Not for use in diagnostic procedureswww.brookslifesciences.com 23
Fully Automated Workflow
For Reserarch Use Only – Not for use in diagnostic procedureswww.brookslifesciences.com 24
Total Time to Data: Real-timeFTE Allotment:Cost: ~$200
Sample Collection
(Clinical Trial)
Sample Processing & PGx
Genotyping(Service Lab)
Sample Storage
(Biorepository)
Data Transfer & Analysis (GWAS, HLA, DMET, etc…)
Biobank Integration
Workflow – Ideal State
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• 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
Advantages of Biobank & Genetic Analysis Integration
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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
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8
Treatment
Patients
Clinical efficacy
No clinical efficacy
Adverse Event
Benc
htoB
edsid
e
Beds
ideto
Benc
h
Patients
Diagnostic Biomarkers
Clinical efficacy
Clinical efficacy
Clinical efficacy
Clinical PGx – Precision Medicine
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A Validated PGx Solution: PMRA
For Reserarch Use Only – Not for use in diagnostic procedureswww.brookslifesciences.com 30
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Tissue
Blood for DNA
Protocolplan
Enrolled patient
ProgrammaticStrategy
Sample CollectionSample/Prep &Biorepository
• Tissue–DNA• Tissue–RNA• Blood --DNA• Blood – RNA• Associated
librariesBlood for RNA
Data Generation
• Tissue WES• Tissue RNAseq• Blood WGS• Blood RNAseq• Blood genotyping
Data Analysisand Results
Outcomes• Real-time program strategy• Treatment combinations• Treatment mechanisms• Understanding value of novel
biomarkers
Molecular Profiling Workflow
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Phase I Phase II Phase III
Inform Discovery
Candidate GenesDrug metabolism,drug targets
Primary DiscoveryGWAS + WES
Genetic Marker/ Positive Result
YES
NO
Stratified Trial Enriched for responders
Continued Discovery GWAS, targeted genotyping, +/- WES
CLINICALPROGRAM Biomarker Validation, Mechanism of Action, Novel Biomarkers, New Targets
GENETICS Genetic variation explains PK variability
Genetic variation Explains variable efficacy
Validation: Phase II GWAS “hit” predicts for response in Phase 3
“New” Routine Genetic Research in Clinical Trials
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Questions…
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Thermo Fisher Scientific and its affiliates are not endorsing, recommending, or promoting any use or application of Thermo Fisher Scientific products presented by third parties during this seminar. Information and materials presented or provided by third parties are provided as-is and without warranty of any kind, including regarding intellectual property rights and reported results. Parties presenting images, text and material represent they have the rights to do so.