Our application for OT-PM-16-003, ?One in a Million ? Precision Medicine Initiative Wisconsin? represents the collaborative efforts of three fully integrated regional healthcare systems to form a virtual state-wide integrated delivery network. The application originates at the Marshfield Clinic Health System (MCHS), one of the most productive and earliest adopters of what has become Precision Medicine. The work of the MCHS has been cited by NIH Director Dr. Francis Collins as a model for the Precision Medicine Initiative (PMI). To ensure comprehensive nearly state-wide coverage of participant health care, MCHS has partnered with the other academic integrated delivery networks in Wisconsin, (University of Wisconsin (UW) and Medical College of Wisconsin (MCW)), that together include 173 clinics, 13 hospitals, insurer partners and 5 Federally Qualified Health Centers (FQHCs). The Blood Center of Wisconsin (BCW) also partners to operate state-wide mobile units of staff and equipment for blood collection that may be purposed for this effort. Through an independent agreement with Aurora Health, the electronic health records of participants recruited by academic and FQHC sites will be made available, ensuring nearly complete coverage of health care records across an entire state, with special emphasis on those populations that are traditionally the most underserved and understudied. The academic sites and FQHC partners have a long history of research cooperation and robust community engagement demonstrated by Clinical and Translational Science Awards (CTSA) ties, the Wisconsin Genome Initiative, reciprocal IRB arrangements, multiple joint grants and other collaborative studies. We have pioneered and implemented data sharing platforms and have demonstrated their usefulness with numerous high impact publications over many years. All three academic centers are leaders in the details of community engagement, recruitment, tracking, return of results and data sharing across various platforms in national and international consortia using large cohorts (e.g., MCHS?s 20,000 participant Personalized Medicine Research Project). A major innovation of this application is that it aligns the major healthcare systems of an entire state to more fully capture each participant?s data wherever participants get their health care. Indeed, 80% of all health care in Wisconsin is captured by our footprint. The State-wide catchment area also includes the oldest, sickest and poorest regions in the US and represent rural and urban areas, including African Americans, Hispanics and Native Americans, all represented as community champions. Through the FQHC partners, the recruiting institutions will achieve the 40% African American, Hispanic and Native American participant rate, with long standing community engagement and history of successful recruitment, including Wisconsin?s 12 Native American Tribes. Lending active support are Community Champions and Community Advisory Boards. A second innovative approach will employ Machine Learning (ML) techniques to optimize recruitment and retention processes. Our scientists have long collaborated on efforts to enhance the breadth and reliability of information extracted from the electronic health record (EHR), using a range of data to identify elements including family pedigrees or the occurrence of clinical events that are susceptible to unreliable coding. These efforts employed state-of-the-art methods including random forests, support vector machines and statistical relational learning, among others. These advanced computational methods will be used to predict those who are most likely to participate and which methods of approach are most effective. A third innovative approach is the planned use of mobile recruitment labs, previously successful with the Survey of the Health of Wisconsin (SHOW). SHOW, began in 2008 provides a novel infrastructure for population health research recruitment, enabling engagement across the state, longitudinal follow-up of participants and community-specific studies. Key assets of SHOW are two mobile units staffed by research and healthcare professionals to facilitate on-site health studies in randomly selected or community-specific participants. SHOW is predicated on community engagement and the response rate has been outstanding (in one study more than 90% of ~4,000 participants consented to follow-up, DNA testing, or blood work). This is true across all racial/ethnic groups, including non-Hispanic Whites, African Americans, Hispanics and Native Americans. The fourth innovative approach is to work with our FQHC partners to recruit traditionally underserved populations. MCHS, UW and MCW will work with FQHC partners (Marshfield Family Health Center, Access Community Health Center, Milwaukee Health Services, Progressive Health Center and 16th Street Community Health Center). Importantly, we are ready to start. We have already informed and engaged our communities through press releases and newsletters. Processes are in place. Volunteers have already asked us to contact them. All the required personnel are trained and SOPs are in place to begin recruitment. We have a productive history of working with partners already funded for PMI cohort recruitment. For several years, we have worked closely (and published) with our colleagues at Northwestern and Columbia through the eMERGE Network and with the University of Pittsburgh through CTSA. Project Director Murray Brilliant has recently served as an advisor to the University of Arizona?s Precision Medicine Program. Thus, we are team-players who are ready, willing and able to be valuable collaborative partners in the effort to build a national engine to transform healthcare under PMI.