Deritei, DávidAird, WilliamErcsey-Ravasz, MáriaRegan, Erzsébet Ravasz2016-04-012016Deritei, Dávid, William C. Aird, Mária Ercsey-Ravasz, and Erzsébet Ravasz Regan. 2016. “Principles of dynamical modularity in biological regulatory networks.” Scientific Reports 6 (1): 21957. doi:10.1038/srep21957. http://dx.doi.org/10.1038/srep21957.2045-2322http://nrs.harvard.edu/urn-3:HUL.InstRepos:26318506Intractable diseases such as cancer are associated with breakdown in multiple individual functions, which conspire to create unhealthy phenotype-combinations. An important challenge is to decipher how these functions are coordinated in health and disease. We approach this by drawing on dynamical systems theory. We posit that distinct phenotype-combinations are generated by interactions among robust regulatory switches, each in control of a discrete set of phenotypic outcomes. First, we demonstrate the advantage of characterizing multi-switch regulatory systems in terms of their constituent switches by building a multiswitch cell cycle model which points to novel, testable interactions critical for early G2/M commitment to division. Second, we define quantitative measures of dynamical modularity, namely that global cell states are discrete combinations of switch-level phenotypes. Finally, we formulate three general principles that govern the way coupled switches coordinate their function.en-USJournal Article2016-04-0110.1038/srep21957