Wisconsin Genomics Initiative Medical Discovery Triangle Wisconsin Medical Research Triangle 1

Marshfield Madison Milwaukee MCRF MCW UW Milwaukee UWSMPH Genetic & Genomic Analysis Diverse Urban & Pediatric Patient Populations High Through-Put Genotyping UW Milwaukee Urban & Environmental Health Community Engagement School of Nursing Marshfield Madison Milwaukee UWSMPH Regenerative Medicine Statistical & Computational Analysis Super-Computing Capability MCRF Rural Cohort Comprised of 20,000 Adults Biomedical Informatics Phenotyping

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.

WGI Goals Phase I Create 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 II Use 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. 4 4

WGI Cores and Major Functions 5 5

Predictive Personalized Medicine Individual Patient G + C + E Repeat for thousands of patients Predictive Personalized Medicine Genetic, Clinical, & Environmental Data Predictive Model for Disease Susceptibility & Treatment Response State-of-the-Art Machine Learning Data picture is from: http://datalib.ed.ac.uk/GRAPHICS/blue_data.gif Machine picture is from Microsoft Clip Art j0423067.jpg j0423067.jpg : http://office.microsoft.com/en-us/clipart/results.aspx?qu=computer&sc=20#168 Pill picture is from Microsoft Clip Art j0403705.jpg : http://office.microsoft.com/en-us/clipart/results.aspx?qu=pill&sc=20 Black stick figure picture is from: http://www.austinkleon.com/wp-content/uploads/2008/02/stick_figure.gif Personalized medicine picture is from: http://www.dnavision.be/images/pharmacogenetics.jpg Personalized Treatment Repeat for hundreds of diseases and treatments 6

Building Accurate Predictive Models ( + & ) = P E C G Complex combinations of variables are required for accurate prediction The more we know about individual patients, greater the probability of prediction

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

Why Wisconsin? 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

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

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 11