title: Computational framework for analysis of prey-prey associations in interaction proteomics identifies novel human protein-protein interactions and networks.
abstract: Large-scale protein-protein interaction data sets have been generated for several species including yeast and human and have enabled the identification, quantification, and prediction of cellular molecular networks. Affinity purification-mass spectrometry (AP-MS) is the preeminent methodology for large-scale analysis of protein complexes, performed by immunopurifying a specific "bait" protein and its associated "prey" proteins. The analysis and interpretation of AP-MS data sets is, however, not straightforward. In addition, although yeast AP-MS data sets are relatively comprehensive, current human AP-MS data sets only sparsely cover the human interactome. Here we develop a framework for analysis of AP-MS data sets that addresses the issues of noise, missing data, and sparsity of coverage in the context of a current, real world human AP-MS data set. Our goal is to extend and increase the density of the known human interactome by integrating bait-prey and cocomplexed preys (prey-prey associations) into networks. Our framework incorporates a score for each identified protein, as well as elements of signal processing to improve the confidence of identified protein-protein interactions. We identify many protein networks enriched in known biological processes and functions. In addition, we show that integrated bait-prey and prey-prey interactions can be used to refine network topology and extend known protein networks.
authors: Center for Proteomics and Bioinformatics, Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors: Sudipto
authors: S
authors: Saha
authors: Jean-Eudes
authors: JE
authors: Dazard
authors: Hua
authors: H
authors: Xu
authors: Rob M
authors: RM
authors: Ewing
mesh_terms: D002846:Chromatography, Affinity; D016000:Cluster Analysis; D030562:Databases, Protein; D006801:Humans; D013058:Mass Spectrometry; D008954:Models, Biological; D025941:Protein Interaction Mapping / Q000379:methods*; D060066:Protein Interaction Maps / Q000502:physiology*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D018709:Statistics, Nonparametric
chemical_list: D011506:Proteins