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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.

SUBMITTER: Deritei D 

PROVIDER: S-EPMC4793241 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Principles of dynamical modularity in biological regulatory networks.

Deritei Dávid D   Aird William C WC   Ercsey-Ravasz Mária M   Regan Erzsébet Ravasz ER  

Scientific reports 20160316


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 demonstra  ...[more]

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