In response to RFA NIDDK RFA-DK-14-503, we propose to develop a public web portal that will aggregate data on human genotypes, phenotypes, and annotations relevant to type 2 diabetes (T2D) and related traits, automate the analysis and interpretation of these data, communicate the results clearly and comprehensively to scientists across biomedical disciplines, and provide an organizational infrastructure for the Accelerating Medicines Partnership in T2D (AMP T2D), a new consortium aiming to empower a wide range of biomedical investigators to use human genetic analysis to accelerate biological understanding and development of new treatments for T2D. As Director of the Data Coordinating Center and Chair of the Steering Committee of the T2D-GENES Consortium, the applicants (Altshuler and Boehnke) have been leaders of the T2D-GENES Consortium, which built a prototype T2D portal that provides access to results and explanations of underlying methods. This prototype includes data on 13,000 exome sequences, 80,000 samples genotyped on the exome array, and meta analyses of 25 genome-wide association studies, allowing users to fetch, filter, sort, and view results from these studies via an intuitive interfae. To expand the portal's data, we will work with the AMP T2D consortium to identify high-quality datasets relevant to T2D, related phenotypes, and functional annotations; develop an administrative and computational infrastructure to collate, store, and manage these datasets; and ensure the data are deposited in this infrastructure. To automate analyses of the data, we will form a group to identify best-practice methods and, where needed, develop new ones; build a software platform to run a series of complex analyses and store their inputs and outputs; and implement these codified statistical methods on the platform. To communicate the results, we will gather user requirements for portal functions; develop a web-based platform and software widgets to facilitate these functions; and design user-friendly queries, visualizations, text, and other features to serve these functions, instantiating them on the portal. To enable collaboration within AMP T2D, we will help define goals for communication and engagement; instantiate standard operating procedures and personnel; and perform administrative functions to support the consortium.
We propose to develop a public web portal that will (a) aggregate data on genotypes, phenotypes, and annotations relevant to type 2 diabetes (T2D) and related traits; (b) automate the analysis and interpretation of these data; (c) communicate the results clearly and comprehensively to scientists across biomedical disciplines; and (d) support a collaborative infrastructure for the AMP T2D-GENES consortium. The goal will be to empower a wide range of biomedical investigators to use human genetic analysis to accelerate understanding of T2D pathophysiology and the development of safe and effective new T2D treatments.
| Fitipaldi, Hugo; McCarthy, Mark I; Florez, Jose C et al. (2018) A Global Overview of Precision Medicine in Type 2 Diabetes. Diabetes 67:1911-1922 |
| Florez, Jose C (2017) Mining the Genome for Therapeutic Targets. Diabetes 66:1770-1778 |
| Florez, Jose C (2017) The pharmacogenetics of metformin. Diabetologia 60:1648-1655 |
| Florez, Jose C (2017) Pharmacogenetics in type 2 diabetes: precision medicine or discovery tool? Diabetologia 60:800-807 |
