title: Identification of Topological Network Modules in Perturbed Protein Interaction Networks.
abstract: Biological networks consist of functional modules, however detecting and characterizing such modules in networks remains challenging. Perturbing networks is one strategy for identifying modules. Here we used an advanced mathematical approach named topological data analysis (TDA) to interrogate two perturbed networks. In one, we disrupted the S. cerevisiae INO80 protein interaction network by isolating complexes after protein complex components were deleted from the genome. In the second, we reanalyzed previously published data demonstrating the disruption of the human Sin3 network with a histone deacetylase inhibitor. Here we show that disrupted networks contained topological network modules (TNMs) with shared properties that mapped onto distinct locations in networks. We define TMNs as proteins that occupy close network positions depending on their coordinates in a topological space. TNMs provide new insight into networks by capturing proteins from different categories including proteins within a complex, proteins with shared biological functions, and proteins disrupted across networks.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Mihaela E
authors.initials: ME
authors.lastname: Sardiu
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Gilmore
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Groppe
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.|Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D060066:Protein Interaction Maps; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D056264:Sin3 Histone Deacetylase and Corepressor Complex / Q000378:metabolism
chemical_list: C483404:INO80 complex, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex