title: Principles of dynamical modularity in biological regulatory networks.
abstract: 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.
authors.affiliation: Hungarian Physics Institute, Faculty of Physics, Babes¸-Bolyai University, Cluj-Napoca 400084, Romania.|Center for Network Science, Central European University, Budapest, 1051, Hungary.
authors.forename: Dávid
authors.initials: D
authors.lastname: Deritei
authors.affiliation: Center for Vascular Biology Research, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Aird
authors.affiliation: Hungarian Physics Institute, Faculty of Physics, Babes¸-Bolyai University, Cluj-Napoca 400084, Romania.
authors.forename: Mária
authors.initials: M
authors.lastname: Ercsey-Ravasz
authors.affiliation: 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.
authors.forename: Erzsébet Ravasz
authors.initials: ER
authors.lastname: Regan
mesh_terms: D000465:Algorithms; D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D016195:G2 Phase / Q000235:genetics; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007700:Kinetics; D008957:Models, Genetic; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics*