title: From the static interactome to dynamic protein complexes: Three challenges.
abstract: Protein interactions and complexes behave in a dynamic fashion, but this dynamism is not captured by interaction screening technologies, and not preserved in protein-protein interaction (PPI) networks. The analysis of static interaction data to derive dynamic protein complexes leads to several challenges, of which we identify three. First, many proteins participate in multiple complexes, leading to overlapping complexes embedded within highly-connected regions of the PPI network. This makes it difficult to accurately delimit the boundaries of such complexes. Second, many condition- and location-specific PPIs are not detected, leading to sparsely-connected complexes that cannot be picked out by clustering algorithms. Third, the majority of complexes are small complexes (made up of two or three proteins), which are extra sensitive to the effects of extraneous edges and missing co-complex edges. We show that many existing complex-discovery algorithms have trouble predicting such complexes, and show that our insight into the disparity between the static interactome and dynamic protein complexes can be used to improve the performance of complex discovery.
authors: Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors: Chern Han
authors: CH
authors: Yong
authors: Limsoon
authors: L
authors: Wong
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D019295:Computational Biology; D057166:High-Throughput Screening Assays / Q000706:statistics & numerical data; D006801:Humans; D008390:Markov Chains; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D060066:Protein Interaction Maps; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000706:statistics & numerical data; D020798:Two-Hybrid System Techniques / Q000706:statistics & numerical data
chemical_list: D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins
keywords: Protein complex; dynamism; protein interaction