There is a wide gap between the generation of large-scale biological data sets and more-detailed, structural and mechanistic studies. However, recent studies that explicitly combine data from systems and structural biological approaches are having a profound effect on our ability to predict how mutations and small molecules affect atomic-level mechanisms, disrupt systems-level networks, and ultimately lead to changes in organismal fitness. In fact, we argue that a shared framework for analysis of nonadditive genetic and thermodynamic responses to perturbations will accelerate the integration of reductionist and global approaches. A stronger bridge between these two areas will allow for a deeper and more-complete understanding of complex biological phenomenon and ultimately provide needed breakthroughs in biomedical research.
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