From systems to structure: bridging networks and mechanism.
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.
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA. james.fraser@ucsf.edu
James S
JS
Fraser
John D
JD
Gross
Nevan J
NJ
Krogan
D000818:Animals; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D060066:Protein Interaction Maps; D049490:Systems Biology; D013816:Thermodynamics