1. THE MURDOCK Study: A Rich Data Resource for Biomarker Discovery and Validation Brian D. Bennett 1, Jessica D. Tenenbaum 1, Victoria Christian 1, Melissa A. Cornish 1, Rowena J. Dolor 2, Ashley A. Dunham 1, Geoffrey S. Ginsburg 3, Virginia B. Kraus 2, Meredith L. Nahm 1, L. Kristin Newby 4,5, Laura P. Svetkey 2,6, Krishna Udayakumar 1, Robert M. Califf 1 1 Duke Translational Medicine Institute, 2 Department of Medicine, Duke, 3 Institute for Genome Science and Policy, Duke, 4 Division of Cardiology, Department of Medicine, Duke, 5 Duke Clinical Research Institute, 6 Stedman Nutrition Center, Duke Contact information Brian D. Bennett, PhD brian.bennett@duke.edu 919-668-9222 Jessica D. Tenenbaum, PhD jessie.tenenbaum@duke.edu 919-668-8811 MURDOCK Study team murdock-study@duke.edu 704-250-5861 Discussion Utility of the tools and data assets generated through each horizon of the MURDOCK Study will be measured in terms of uptake by the research community and generation of currency ranging from impact in peer review publication, to products launched from commercial sector collaboration. The authors invite interested investigators to take full advantage of this rich resource by contacting the MURDOCK Study team (murdock-study@duke.edu) to explore opportunities for collaboration. Acknowledgements MURDOCK Study Team The population and health care providers of Kannapolis and Cabarrus County, NC. Funding Sources The MURDOCK Study is funded by a gift from the David H. Murdock Institute for Business and Culture and receives support from NCRR: UL1 RR024128. Informatics as a bridge Enabling novel analyses The generation of multi-modal omics datasets on the same samples will enable a systems biology approach to biomarker discovery through integrative analyses. For example, genomic and transcriptomic data may be combined to enable “eSNP” analysis. Abstract The MURDOCK study is an ongoing initiative to reclassify disease based on underlying molecular mechanism. The Study comprises a series of stages or “horizons”. Horizon 1 involved the generation and analysis of omics data in four existing disease cohorts. Horizon 1.5 is a community- based registry and biorepository. Horizon 2 leverages the Horizon 1.5 registry for validation studies and recruitment of target populations, and Horizon 3 expands the scope of the study to include populations from around the region and the world. Genomic, transcriptomic, metabol- omic, and/ or proteomic data has been generated for a number of disease-focused cohorts, and data collection is ongoing for additional disease areas and healthy controls from a 50,000 person community- based registry (9000 enrolled to date). This valuable data resource is available for translational research collaborations. Overview of Horizon 1 Studies Therapeutic Area Cardio- vascular disease Liver disease OsteoarthritisObesity Targeted Metabolomics 2023 plasma-- 500 plasma and serum Discovery Proteomics 60 plasma96 serum 48 urine, 14 synovial fluids - Targeted Proteomics 500 plasma96 serum108 serum- Genome-Wide Genotype 2023961258- Gene Expression 500 PaxGene RNA --- Horizon 1.5: The Registry Horizon 1.5 entails a volunteer registry where participants provide clinical and demographic information along with blood and urine samples. There are currently over 9000 participants enrolled, with an ultimate goal of 50,000 participants. This registry includes self-reported information, baseline biospecimens, annual follow-up, access to electronic health records, and permission to re- contact. (19 additional diseases not shown) Horizon 1 In Horizon 1, investigators generated metabolomics, proteomics, gene expression, and genotype data for existing cohorts from several different disease areas. These data, along with clinical outcomes, were used to perform biomarker discovery to predict events, disease progression, and response to therapy. The MURDOCK Integrated Data Repository (MIDR) is the informatics core of the study, and provides the ability to store, manage, retrieve, and query study- related data and metadata. Version 1.0 contains clinical data only from Horizon 1. Version 2 planning is underway.