title: An integrative approach to inferring biologically meaningful gene modules.
abstract: BACKGROUND
  The ability to construct biologically meaningful gene networks and modules is critical for contemporary systems biology. Though recent studies have demonstrated the power of using gene modules to shed light on the functioning of complex biological systems, most modules in these networks have shown little association with meaningful biological function. We have devised a method which directly incorporates gene ontology (GO) annotation in construction of gene modules in order to gain better functional association.
  
  
  RESULTS
  We have devised a method, Semantic Similarity-Integrated approach for Modularization (SSIM) that integrates various gene-gene pairwise similarity values, including information obtained from gene expression, protein-protein interactions and GO annotations, in the construction of modules using affinity propagation clustering. We demonstrated the performance of the proposed method using data from two complex biological responses: 1. the osmotic shock response in Saccharomyces cerevisiae, and 2. the prion-induced pathogenic mouse model. In comparison with two previously reported algorithms, modules identified by SSIM showed significantly stronger association with biological functions.
  
  
  CONCLUSIONS
  The incorporation of semantic similarity based on GO annotation with gene expression and protein-protein interaction data can greatly enhance the functional relevance of inferred gene modules. In addition, the SSIM approach can also reveal the hierarchical structure of gene modules to gain a broader functional view of the biological system. Hence, the proposed method can facilitate comprehensive and in-depth analysis of high throughput experimental data at the gene network level.
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109, USA.
authors.forename: Ji-Hoon
authors.initials: JH
authors.lastname: Cho
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: David J
authors.initials: DJ
authors.lastname: Galas
mesh_terms: D000465:Algorithms; D000818:Animals; D053263:Gene Regulatory Networks / Q000235:genetics*; D051379:Mice; D008957:Models, Genetic; D058977:Molecular Sequence Annotation / Q000379:methods*; D009997:Osmotic Pressure; D017096:Prion Diseases / Q000235:genetics; D060066:Protein Interaction Maps / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D049490:Systems Biology / Q000379:methods*