Major advances in genome science and molecular technologies provide new opportunities at the interface between basic biological research and medical practice. The unprecedented completeness, accuracy, and volume of genomic and molecular data necessitate a new kind of computational biology for translational research. Key challenges are standardization of data capture and communication, organization of easily accessible repositories, and algorithms for integrated analysis based on heterogeneous sources of information. Also required are new ways of using complementary clinical and biological data, such as computational methods for predicting disease phenotype from molecular and genetic profiling. New combined experimental and computational methods hold the promise of more accurate diagnosis and prognosis as well as more effective prevention and therapy.