Prioritizing disease candidate genes by a gene interconnectedness-based approach

Chia Lang Hsu, Yen Hua Huang, Chien Ting Hsu, Ueng Cheng Yang*

*Corresponding author for this work

Research output: Contribution to conferencePaperpeer-review

35 Scopus citations


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.


Conference10th International Conference on Bioinformatics and 1st ISCB Asia Joint Conference 2011: Computational Biology, InCoB 2011/ISCB-Asia 2011
CityKuala Lumpur


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