title: Bridging topological and functional information in protein interaction networks by short loops profiling.
abstract: Protein-protein interaction networks (PPINs) have been employed to identify potential novel interconnections between proteins as well as crucial cellular functions. In this study we identify fundamental principles of PPIN topologies by analysing network motifs of short loops, which are small cyclic interactions of between 3 and 6 proteins. We compared 30 PPINs with corresponding randomised null models and examined the occurrence of common biological functions in loops extracted from a cross-validated high-confidence dataset of 622 human protein complexes. We demonstrate that loops are an intrinsic feature of PPINs and that specific cell functions are predominantly performed by loops of different lengths. Topologically, we find that loops are strongly related to the accuracy of PPINs and define a core of interactions with high resilience. The identification of this core and the analysis of loop composition are promising tools to assess PPIN quality and to uncover possible biases from experimental detection methods. More than 96% of loops share at least one biological function, with enrichment of cellular functions related to mRNA metabolic processing and the cell cycle. Our analyses suggest that these motifs can be used in the design of targeted experiments for functional phenotype detection.
authors.affiliation: 1] Department of Haematological Medicine, King's College London, UK [2] Randall Division of Cell and Molecular Biophysics, King's College London, UK.
authors.forename: Sun Sook
authors.initials: SS
authors.lastname: Chung
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pandini
authors.affiliation: 1] Department of Mathematics, King's College London, UK [2] Institute for Mathematical and Molecular Biomedicine, King's College London, UK.
authors.forename: Alessia
authors.initials: A
authors.lastname: Annibale
authors.affiliation: 1] Department of Mathematics, King's College London, UK [2] Institute for Mathematical and Molecular Biomedicine, King's College London, UK.
authors.forename: Anthony C C
authors.initials: AC
authors.lastname: Coolen
authors.affiliation: Department of Haematological Medicine, King's College London, UK.
authors.forename: N Shaun B
authors.initials: NS
authors.lastname: Thomas
authors.affiliation: 1] Randall Division of Cell and Molecular Biophysics, King's College London, UK [2] Institute for Mathematical and Molecular Biomedicine, King's College London, UK.
authors.forename: Franca
authors.initials: F
authors.lastname: Fraternali
mesh_terms: D000465:Algorithms; D006801:Humans; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011506:Proteins