title: Links between critical proteins drive the controllability of protein interaction networks.
abstract: Focusing on the interactomes of Homo sapiens, Saccharomyces cerevisiae, and Escherichia coli, we investigated interactions between controlling proteins. In particular, we determined critical, intermittent, and redundant proteins based on their tendency to participate in minimum dominating sets. Independently of the organisms considered, we found that interactions that involved critical nodes had the most prominent effects on the topology of their corresponding networks. Furthermore, we observed that phosphorylation and regulatory events were considerably enriched when the corresponding transcription factors and kinases were critical proteins, while such interactions were depleted when they were redundant proteins. Moreover, interactions involving critical proteins were enriched with essential genes, disease genes, and drug targets, suggesting that such characteristics may be key for the detection of novel drug targets as well as assess their efficacy.
authors.affiliation: Department of Computer Science, University of Miami, Coral Gables, FL, USA.|Center of Computational Sciences, University of Miami, Coral Gables, FL, USA.|Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
authors.forename: Stefan
authors.identifier: http://orcid.org/0000-0001-8916-6522
authors.initials: S
authors.lastname: Wuchty
authors.affiliation: Department of Computer Science, University of Miami, Coral Gables, FL, USA.
authors.forename: Toni
authors.initials: T
authors.lastname: Boltz
authors.affiliation: Department of Computer Science, University of Miami, Coral Gables, FL, USA.
authors.forename: Hande
authors.initials: H
authors.lastname: Küçük-McGinty
keywords: Critical proteins; Network control; Protein-protein interactions