Wisconsin Genomics Initiative

Wisconsin Medical Research Triangle

WisconsinMedical

DiscoveryTriangle

MCW•Genetic & Genomic Analysis• Diverse Urban & Pediatric

Patient Populations•High Through-Put Genotyping

UW Milwaukee• Urban & Environmental Health

• Community Engagement• School of Nursing

Marshfield

MadisonMilwaukee

UWSMPH• Regenerative Medicine

•Statistical & Computational Analysis

• Super-Computing Capability

MCRF• Rural Cohort

Comprised of 20,000 Adults

•Biomedical Informatics• Phenotyping

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WGI Vision

Vision: To be able to predict for individual patients in a clinical setting the risks of disease susceptibility and treatment response using the combined power of cutting edge genetic, phenotypic, and environmental analyses.

Thereby, making the promise of personalized medicine a reality for the citizens of Wisconsin and beyond.

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WGI Goals

• Phase ICreate the medical research infrastructure to build and test a unique scientific platform that is capable of predicting disease susceptibility and treatment response to a high degree of accuracy; and to make it widely available to scientists across the country.

• Phase IIUse this unique scientific platform for discovery in multiple disease areas and treatment methods; and to improve its capability by expanding research cohorts, increasing the number of genetic markers, increasing the amount of environmental and clinical data, and improving the computational algorithms.

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Bio-Repository and Bio-Specimen Core (MCRF) Maintain & provide high quality biologic

samples Develop an analyte database from PMRP

serum samples Develop methods to harmonize inclusion

of new bio-repositories

WGI Data Warehouse and User Interface Core (MCRF) Maintain genetic, phenotypic, and

environmental information databases Develop and maintain the search engines

to use data efficiently for discovery Maintain interface with scientists using

WGI data Genetic & Genomic Analysis Core (MCW) Conduct genetic & genomic analysis Identify 1,000,000 genetic markers on

each of the 20,000 PMRP subjects

Statistical & Computational Analysis Core (UWSMPH) Build predictive computational models Conduct computational analysis for initial

predictive studies Conduct a genome wide association

study (GWAS) Phenotyping Core (MCRF) Validate target phenotypes and selected

clinical/environmental data on PMRP cohort using electronic medical record

Develop data resources and tools to enhance phenotyping efforts

Urban Personalized Healthcare Cohort Core (MCW & UW-Milwaukee) Plan the enrollment of an urban,

economically diverse, ethnically diverse cohort for Phase II implementation

Conduct population & community education

Establish a Community Advisory Board

WGI Cores and Major Functions

Predictive PersonalizedMedicine

Repeat for hundreds of diseases and treatments

Repeat for thousands of patients

PersonalizedTreatment

Individual Patient

G + C + E

Predictive Model for

Disease Susceptibility& TreatmentResponseState-of-the-Art

Machine Learning

Genetic,Clinical,

&Environmental

Data

Building Accurate Predictive Models

Complex combinations of variables are required for accurate prediction The more we know about individual patients, greater the probability of prediction

Genetic + (Environmental Factors & Clinical Attributes) = Phenotype 1,000,000 SNPs will hit

or be close to most medically relevant genetic markers

Smoking Diet Exercise Alcohol Residence Occupation Socio-economic status Chemical exposure

Disease diagnoses Exposure to:

- Viruses - Bacteria - Drugs not involved in medical

treatment Treatment (medical)

- Current medications - Past medications - Vaccinations - Other

Treatment (procedures) Physiologic parameters

- Chemical measures (e.g., HDL, cholesterol)

- Physical measures (e.g., weight, height)

- Electrical activity (e.g., EKG) - Imagining

Cardiovascular diseases Diabetes Obesity Stroke Cancer Allergies and Asthma Alzheimer’s Childhood illnesses &

developmental disorders Eye diseases Other

(+ & )=PP

EE CCGG

What Makes WGI Unique Among Large Genetic Research Projects?

• Is a natural laboratory• PMRP is a population-based study with a stable population• PMRP cohort is consented for ongoing clinical data collection

over a lifetime through Electronic Health Record• High level of compliance for recommended health screenings to

classify controls• Genome Wide Association Studies using Machine Learning• Through the Governor’s eHealth Care Quality and Patient Safety

Initiative, Wisconsin will be among the first states to have statewide adoption of electronic health record standards and capability for statewide health information exchanges

• As a natural laboratory and with eHealth exchange capability, WGI can expand dramatically and efficiently beyond the planned 50,000-person combined rural, urban, and children’s cohorts

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• Approximately 2% of US population providing size, manageability, and representativeness

• With additional subject recruitment in Milwaukee, WGI will have breadth of research cohorts– Rural and Urban– Northern European and Minorities– Adults and Children– Economically advantaged and disadvantaged

• A value-added project, does not start from scratch– The major elements of the strategy are in place, including the DNA

samples, genotyping capability, phenotyping protocols, machine learning algorithms, and super-computing capabilities

– Can begin immediately upon funding and will have meaningful results within 2 years

• WGI and the Wisconsin Action Plan for Health Care Quality and Safety are mutually supportive

• Intellectual capital strong and able to grow with an influx of resources

Why Wisconsin?

Benefits to the State

• Leadership in an international movement to transform health care delivery using the human genome

• Save lives and improve medical care• Reduce health care costs• Develop heath care education programs here first, drawing talent

from all over the globe• Strengthen the economy

• Increased research dollars • Creation of “spin-off” companies and new high tech jobs• Attractive location for pharmaceutical companies

• Additional benefits for urban populations and underserved communities

– Addresses unique health care issues of urban populations– Increases access to health care for all by making it more affordable – Studies those chronic diseases that are increasingly devastating families in

underserved communities

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Summary

• Wisconsin has in its Medical Research Triangle all of the resources necessary to make a major advancement in the application of genetic science to human health

• The Wisconsin Genomics Initiative is positioned to make the promise of personalized medicine and personalized health care a reality

• The Wisconsin Genomics Initiative aligns with the priorities of the National Institutes of Health, the US Department of Health and Human Services, and the State of Wisconsin

• The Wisconsin Genomics Initiative offers a rare opportunity to bring the UW School of Medicine and Public Health, the Medical College of Wisconsin, UW-Milwaukee, and Marshfield Clinic together to meet important scientific and public health needs