title: Compensatory interactions to stabilize multiple steady states or mitigate the effects of multiple deregulations in biological networks.
abstract: Complex diseases can be modeled as damage to intracellular networks that results in abnormal cell behaviors. Network-based dynamic models such as Boolean models have been employed to model a variety of biological systems including those corresponding to disease. Previous work designed compensatory interactions to stabilize an attractor of a Boolean network after single node damage. We generalize this method to a multinode damage scenario and to the simultaneous stabilization of multiple steady state attractors. We classify the emergent situations, with a special focus on combinatorial effects, and characterize each class through simulation. We explore how the structural and functional properties of the network affect its resilience and its possible repair scenarios. We demonstrate the method's applicability to two intracellular network models relevant to cancer. This work has implications in designing prevention strategies for complex disease.
authors.affiliation: Department of Physics, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Physics, Pennsylvania State University, University Park, Pennsylvania 16802, USA.|Department of Physics, Washington College, Chestertown, Maryland 21620, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Campbell
authors.affiliation: Department of Physics, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Réka
authors.initials: R
authors.lastname: Albert
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D053263:Gene Regulatory Networks / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000503:physiopathology