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Sci Rep. 2016 Mar 16;6:21957. doi: 10.1038/srep21957.

Principles of dynamical modularity in biological regulatory networks.

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Hungarian Physics Institute, Faculty of Physics, Babes¸-Bolyai University, Cluj-Napoca 400084, Romania.
Center for Network Science, Central European University, Budapest, 1051, Hungary.
Center for Vascular Biology Research, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Biochemistry and Molecular Biology, The College of Wooster, Wooster, OH 44691, USA.


Intractable 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.

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