pharmacogenomics analysis laboratory
DESCRIPTION
PHARMACOGENOMICS ANALYSIS LABORATORY. Cooperative Studies Program (CSP) Office of Research & Development, Department of Veterans Affairs Central Arkansas Veterans Healthcare System (CAVHS) Little Rock, AR. CSP ORGANIZATION. VETERANS HEALTH ADMIN Office of Research & Development. - PowerPoint PPT PresentationTRANSCRIPT
PHARMACOGENOMICS ANALYSIS LABORATORY
Cooperative Studies Program (CSP)Office of Research & Development,
Department of Veterans Affairs
Central Arkansas Veterans Healthcare System (CAVHS)
Little Rock, AR
CSP ORGANIZATION
VETERANS HEALTH ADMINVETERANS HEALTH ADMINOffice of Research &Office of Research &
DevelopmentDevelopment
VETERANS HEALTH ADMINVETERANS HEALTH ADMINOffice of Research &Office of Research &
DevelopmentDevelopment
BiomedicalLaboratory
R&D
RehabilitationR&D
Clinical Science
R&D
Health Services
R&D
Cooperative Studies Program
Pharmacogenomics Analysis Laboratory (PAL)
CSP MISSION
To advance the health and care of Veterans through collaborative research studies that produce innovative and effective solutions to national healthcare problems.
CSP OVERVIEW
• CSP is a national infrastructure for sponsoring, developing & executing: Multi-site clinical trials Epidemiological & population research Genomics research
• First Cooperative Study conducted in 1940s on streptomycin for treating tuberculosis in WWII veterans Program formally established in 1972
• Over 175 clinical trials and observational studies completed including landmark studies in cardiovascular disease / cardiovascular surgery, infectious diseases, surgery, gastroenterology, mental health, oncology, and endocrinology.
CSP CENTER LOCATIONS
West Haven, CT
Seattle, WA
Palo Alto, CA
Albuquerque, NM
Durham, NC
Hines, IL
Washington, DC
Perry Point, MD
Boston, MA
Little Rock, AR
VA Genomic Medicine Program
• In 2006, the Department of Veterans Affairs launched the Genomic Medicine Program:
to examine the potential of emerging genomic technologies
to optimize medical care for veterans to enhance the development of tests and
treatments for relevant diseases
• Genomic Medicine Program Advisory Committee
• Veterans’ Consultation Project 83% supported; 71% willing to participate
• Scientific Projects Investigator-initiated Large scale cohorts (SMI, PTSD, ALS)
Million Veteran Program (non-disease based)
Genomic Medicine Program Con’t
Infrastructure Development
Expansion of Biorepository CSP DNA Bank (~30,000 samples) Expansion to ~4M; robotic store; automation
IT and Informatics Genomic Information System for Integrated
Sciences(GenISIS) Pharmacogenomics Laboratory (PAL)
Established in 2007
Pharmacogenomics Analysis
Laboratory (PAL)
•CLIA88 approved laboratory with capacity to conduct medium to high throughput genotyping and gene expression assays.
•Support ongoing and future pharmacogenomics observational studies and clinical trials.
•Improving treatment of most illnesses by reducing toxicity and increasing efficacy of drugs by facilitating optimal treatment selection, appropriate dose individualization, and drug discovery.
PAL Organizational FlowChart
Dr. Steven A. Schichman
PAL Director
Weleetka Carter, Maria Winters, Angie Stone
DIRECTOR Steven A. Schichman, M.D., Ph.D.
DNA Purification & Quantification
RNA Purification & Quantification
Gene Expression
miRNA
SNP Genotyping
Copy Number, EpiGenetic Events
Data Analysis & Final Reports
Protein Analysis
Protein Quantification
PAL
ABI Taqman, Illumina iScan & BeadXpress
ABI Taqman, Illumina iScan & BeadXpress
ABI Taqman, Illumina iScan & BeadXpress
ABI Taqman
Illumina BeadXpressNanoDrop UV/Vis, Agilent Bioanalyzer
NanoDrop UV/Vis, Agilent Bioanalyzer, Biotek Plate Reader (PicoGreen Fluorescence)TaqMan RNAse P
NanoDrop UV/Vis, Agilent Bioanalyzer, Biotek Plate Reader (RiboGreen Fluorescence)TaqMan RNAse P
CAVHS
miRNA
ABI 7900HT TaqMan System
The ABI 7900HT (Applied Biosystems, Inc., Foster City, CA) is a PCR-based, real-time thermal cycling instrument with fluorescence detection for low-to-moderate throughput genotyping and gene expression
Applications Supported by ABI7900HT TaqMan
Genotyping by Allelic Discrimination Real-Time Quantification
Gene Expression Copy Number Variation
Illumina iScan System
•iScan microarray scanner (Illumina, Inc., San Diego, CA) is a confocal laser scanner with dual fluorescent channels for imaging Illumina’s array-based genetic analysis products. •Automation with the AutoLoader2 provides high-throughput scanning.
Copy Number Variation: Discovery and AnalysisBeadChip Genotyping Array: Whole-Genome SNP Analyses, Cytogenetic Analysis, Linkage Profiling
0 10000 20000 30000Control_AVG_Signal
Gene Expression
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20000
30000
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Whole-Genome Expression Profiling, Differ-ential Gene Expression, microRNA profiling
Whole-Genome Methylation Analyses, Differential Methylation, Dendrograms (Cluster Analysis)
iScan Applications
Illumina iScan Array Products
Illumina BeadXpress System
Illumina’s BeadXpress Reader is a dual-color laser detection system for custom low- to mid-plex genotyping, methylation analysis, SNP detection and protein screening.
ADME Core Panel for Pharmacogenetic Genotyping
► Investigate genetic associations to drug
• Response• Dosing• Safety
► Personalized Medicine
*Absorption, Distribution, Metabolism, and Excretion
VeraCode ADME Core Panel
ADME Core (34 genes, 184 markers)
ABCB1 CYP2C9 NAT1 SULT1A1
ABCC2 CYP2D6 NAT2 TPMT
ABCG2 CYP2E1 SLC15A2 UGT1A1
CYP1A1 CYP3A4 SLC22A1 UGT2B15
CYP1A2 CYP3A5 SLC22A2 UGT2B17
CYP2A6 DPYD SLC22A6 UGT2B7
CYP2B6 GSTM1 SLCO1B1 VKORC1
CYP2C19 GSTP1 SLCO1B3
CYP2C8 GSTT1 SLCO2B1
>95% Pharma ADME Core List: www.pharmaadme.org
IT Requirements
• Large capacity Terabyte Servers
• 64-Bit Computers
• GenomeStudio Software Suite
• Statistical Discovery Software
CSP 500b: Genetic Epidemiology of Amyotrophic
Lateral Sclerosis (ALS)• GWAS analysis by Affymetrix & Illumina platforms
completed• 1200 ALS patients ; 400 Controls
• Analysis of data ongoing at the Durham VA and Duke University
CSP Study Update
Durham VA Medical Center
North Carolina
Principal Investigators in CSP500b:Durham VAMC and Duke University Medical Center, NC
Eugene Z. Oddone, M.D., M.H.S.Silke Schmidt, Ph.D.Dawn Provenzale, M.D., M.S.Michael A. Hauser, Ph.D.
Boston MAVERIC and Tissue Core Biorepository, MAMary Brophy, M.D.Donald E. Humphries, Ph.D.
Summary
• PAL serves as a national VA resource for various molecular, genetic and genomic analyses (low to high throughput)
• Isolation to data analysis
• CLIA certified