title: Integration of molecular network data reconstructs Gene Ontology.
abstract: BACKGROUND
  Recently, a shift was made from using Gene Ontology (GO) to evaluate molecular network data to using these data to construct and evaluate GO. Dutkowski et al. provide the first evidence that a large part of GO can be reconstructed solely from topologies of molecular networks. Motivated by this work, we develop a novel data integration framework that integrates multiple types of molecular network data to reconstruct and update GO. We ask how much of GO can be recovered by integrating various molecular interaction data.
  
  
  RESULTS
  We introduce a computational framework for integration of various biological networks using penalized non-negative matrix tri-factorization (PNMTF). It takes all network data in a matrix form and performs simultaneous clustering of genes and GO terms, inducing new relations between genes and GO terms (annotations) and between GO terms themselves. To improve the accuracy of our predicted relations, we extend the integration methodology to include additional topological information represented as the similarity in wiring around non-interacting genes. Surprisingly, by integrating topologies of bakers' yeasts protein-protein interaction, genetic interaction (GI) and co-expression networks, our method reports as related 96% of GO terms that are directly related in GO. The inclusion of the wiring similarity of non-interacting genes contributes 6% to this large GO term association capture. Furthermore, we use our method to infer new relationships between GO terms solely from the topologies of these networks and validate 44% of our predictions in the literature. In addition, our integration method reproduces 48% of cellular component, 41% of molecular function and 41% of biological process GO terms, outperforming the previous method in the former two domains of GO. Finally, we predict new GO annotations of yeast genes and validate our predictions through GIs profiling.
  
  
  METHODS
  Supplementary Tables of new GO term associations and predicted gene annotations are available at http://bio-nets.doc.ic.ac.uk/GO-Reconstruction/.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Computing, Imperial College London SW7 2AZ, UK.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Gligorijević
authors.affiliation: Department of Computing, Imperial College London SW7 2AZ, UK.
authors.forename: Vuk
authors.initials: V
authors.lastname: Janjić
authors.affiliation: Department of Computing, Imperial College London SW7 2AZ, UK.
authors.forename: Nataša
authors.initials: N
authors.lastname: Pržulj
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D015870:Gene Expression; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D058977:Molecular Sequence Annotation; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism