title: Extending signaling pathways with protein-interaction networks. Application to apoptosis.
abstract: Cells exploit signaling pathways during responses to environmental changes, and these processes are often modulated during disease. Particularly, relevant human pathologies such as cancer or viral infections require downregulating apoptosis signaling pathways to progress. As a result, the identification of proteins responsible for these changes is essential for the diagnostics and development of therapeutics. Transferring functional annotation within protein interaction networks has proven useful to identify such proteins, although this is not a trivial task. Here, we used different scoring methods to transfer annotation from 53 well-studied members of the human apoptosis pathways (as known by 2005) to their protein interactors. All scoring methods produced significant predictions (compared to a random negative model), but its number was too large to be useful. Thus, we made a final prediction using specific combinations of scoring methods and compared it to the proteins related to apoptosis signaling pathways during the last 5 years. We propose 273 candidate proteins that may be relevant in apoptosis signaling pathways. Although some of them have known functions consistent with their proposed apoptotsis involvement, the majority have not been annotated yet, leaving room for further experimental studies. We provide our predictions at http://sbi.imim.es/web/Apoptosis.php.
authors.affiliation: Structural Bioinformatics Group, GRIB, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Planas-Iglesias
authors.forename: Emre
authors.initials: E
authors.lastname: Guney
authors.forename: Javier
authors.initials: J
authors.lastname: García-García
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Robertson
authors.forename: Sobia
authors.initials: S
authors.lastname: Raza
authors.forename: Tom C
authors.initials: TC
authors.lastname: Freeman
authors.forename: Peter
authors.initials: P
authors.lastname: Ghazal
authors.forename: Baldo
authors.initials: B
authors.lastname: Oliva
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D019295:Computational Biology / Q000379:methods; D006801:Humans; D008954:Models, Biological; D060066:Protein Interaction Maps / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*