title: Prioritizing disease candidate genes by a gene interconnectedness-based approach.
abstract: BACKGROUND
  Genome-wide disease-gene finding approaches may sometimes provide us with a long list of candidate genes. Since using pure experimental approaches to verify all candidates could be expensive, a number of network-based methods have been developed to prioritize candidates. Such tools usually have a set of parameters pre-trained using available network data. This means that re-training network-based tools may be required when existing biological networks are updated or when networks from different sources are to be tried.
  
  
  RESULTS
  We developed a parameter-free method, interconnectedness (ICN), to rank candidate genes by assessing the closeness of them to known disease genes in a network. ICN was tested using 1,993 known disease-gene associations and achieved a success rate of ~44% using a protein-protein interaction network under a test scenario of simulated linkage analysis. This performance is comparable with those of other well-known methods and ICN outperforms other methods when a candidate disease gene is not directly linked to known disease genes in a network. Interestingly, we show that a combined scoring strategy could enable ICN to achieve an even better performance (~50%) than other methods used alone.
  
  
  CONCLUSIONS
  ICN, a user-friendly method, can well complement other network-based methods in the context of prioritizing candidate disease genes.
authors.affiliation: Institute of Biomedical Informatics, National Yang-Ming University, Taipei City, Taiwan 11221, Republic of China.
authors.forename: Chia-Lang
authors.initials: CL
authors.lastname: Hsu
authors.forename: Yen-Hua
authors.initials: YH
authors.lastname: Huang
authors.forename: Chien-Ting
authors.initials: CT
authors.lastname: Hsu
authors.forename: Ueng-Cheng
authors.initials: UC
authors.lastname: Yang
mesh_terms: D000465:Algorithms; D030541:Databases, Genetic; D004194:Disease / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods*; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans