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The exponentially increasing amounts of biological data along with comparable advances in computing power are making possible the construction of quantitative, predictive biological systems models. This development could revolutionize those biology-based fields of science. To assist this transformation, the U.S. Department of Energy asked the National Research Council to recommend mathematical research activities to enable more effective use of the large amounts of existing genomic information and the structural and functional genomic information being created. The resulting study is a broad, scientifically based view of the opportunities lying at the mathematical science and biology interface. The book provides a review of past successes, an examination of opportunities at the various levels of biological systems - from molecules to ecosystems - an analysis of cross-cutting themes, and a set of recommendations to advance the mathematics-biology connection that are applicable to all agencies funding research in this area.