This funding opportunity announcement (FOA) is for projects from individual-investigators or small groups to collaborate with the NIH Roadmap for Medical Research National Centers for Biomedical Computing (NCBCs). For a description of the NCBCs see http://www.bisti.nih.gov/ncbc/. The intention of the collaborating projects is to engage researchers across the nation in building an excellent biomedical computing environment, using the computational tools and biological and behavioral application drivers of the funded NCBCs as foundation stones. This FOA is intended to support exploratory biomedical informatics and computational biology research—applications should be innovative, with high risk/high impact in new areas that are lacking preliminary data or development. Applications for R21 awards should describe projects distinct from those supported through the traditional R01 mechanism. For example, long-term projects, or projects designed to increase knowledge in a well-established area will not be considered for R21 awards.