title: Weighted mutual information analysis substantially improves domain-based functional network models.
abstract: Functional protein-protein interaction (PPI) networks elucidate molecular pathways underlying complex phenotypes, including those of human diseases. Extrapolation of domain-domain interactions (DDIs) from known PPIs is a major domain-based method for inferring functional PPI networks. However, the protein domain is a functional unit of the protein. Therefore, we should be able to effectively infer functional interactions between proteins based on the co-occurrence of domains.
  
  
  
  Here, we present a method for inferring accurate functional PPIs based on the similarity of domain composition between proteins by weighted mutual information (MI) that assigned different weights to the domains based on their genome-wide frequencies. Weighted MI outperforms other domain-based network inference methods and is highly predictive for pathways as well as phenotypes. A genome-scale human functional network determined by our method reveals numerous communities that are significantly associated with known pathways and diseases. Domain-based functional networks may, therefore, have potential applications in mapping domain-to-pathway or domain-to-phenotype associations.
  
  
  
  Source code for calculating weighted mutual information based on the domain profile matrix is available from www.netbiolab.org/w/WMI CONTACT: Insuklee@yonsei.ac.kr
  
  
  
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Shim
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Insuk
authors.initials: I
authors.lastname: Lee
mesh_terms: D000465:Algorithms; D019295:Computational Biology; D030562:Databases, Protein; D006801:Humans; D058977:Molecular Sequence Annotation; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D011506:Proteins
chemical_list: D011506:Proteins