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In this talk we will discuss the role that high-performance computing and advanced data systems play in accelerating the transition of biology from a science primarily focused on description and explanation to a new science focused on systems level understanding and data driven predictive theories. We will discuss the role that genomics driven biological models are playing in reshaping what is possible in biological analysis and how high-performance computing technologies are playing a critical role in enabling new types of biological investigations. We will outline how we go from raw DNA sequence data to predictive whole genome models of biological phenotype and how automated annotation and analysis systems are enabling small biological labs to do things that were not possible at any scale just a few years ago. We will project how the increases in computing capability coupled with the increases in biological sequence generation throughput and the rise of data integration methods will result in a rapid expansion of our understanding. If time permits, we will discuss the impact that predictive biological models can have on health, energy, the environment and science.