Network stress: a wiring diagram of whole stress genes

Stress sensitivity and tolerance are the consequences of coordinated regulation by multiple genes. Existing genetic tools can identify key genes that mediate metabolic and physiological processes sensing and perceiving stresses. However, it has become increasingly clear that the end-point phenotype of stress response resulting from these intermediate processes involves intricate but well-coordinated networks constituted by a large array of genes. Here, we describe an emerging functional game-graph theory to coalesce all genes from mapping or association studies into genetic interaction networks. These networks enable geneticists to trace, visualize, and interrogate the precise roadmap of how each gene acts and interacts with every other gene to mediate stress response. By shifting reductionist thinking to a holistic, systems-oriented thinking, this theory overcomes a major challenge of elucidating the detailed genetic architecture of stress response.