title: Functional coherence in domain interaction networks.
abstract: BACKGROUND
  Extracting functional information from protein-protein interactions (PPI) poses significant challenges arising from the noisy, incomplete, generic and static nature of data obtained from high-throughput screening. Typical proteins are composed of multiple domains, often regarded as their primary functional and structural units. Motivated by these considerations, domain-domain interactions (DDI) for network-based analyses have received significant recent attention. This article performs a formal comparative investigation of the relationship between functional coherence and topological proximity in PPI and DDI networks. Our investigation provides the necessary basis for continued and focused investigation of DDIs as abstractions for functional characterization and modularization of networks.
  
  
  RESULTS
  We investigate the problem of assessing the functional coherence of two biomolecules (or segments thereof) in a formal framework. We establish essential attributes of admissible measures of functional coherence, and demonstrate that existing, well-accepted measures are ill-suited to comparative analyses involving different entities (i.e. domains versus proteins). We propose a statistically motivated functional similarity measure that takes into account functional specificity as well as the distribution of functional attributes across entity groups to assess functional similarity in a statistically meaningful and biologically interpretable manner. Results on diverse data, including high-throughput and computationally predicted PPIs, as well as structural and computationally inferred DDIs for different organisms show that: (i) the relationship between functional similarity and network proximity is captured in a much more (biologically) intuitive manner by our measure, compared to existing measures and (ii) network proximity and functional similarity are significantly more correlated in DDI networks than in PPI networks, and that structurally determined DDIs provide better functional relevance as compared to computationally inferred DDIs.
authors.affiliation: Department of Computer Science, Purdue University, West Lafayette, IN, USA. jpandey@cs.purdue.edu
authors.forename: Jayesh
authors.initials: J
authors.lastname: Pandey
authors.forename: Mehmet
authors.initials: M
authors.lastname: Koyutürk
authors.forename: Shankar
authors.initials: S
authors.lastname: Subramaniam
authors.forename: Ananth
authors.initials: A
authors.lastname: Grama
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D008954:Models, Biological; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D020543:Proteome