J. Comput. Biol. - Vavien: an algorithm for prioritizing candidate disease genes based on topological similarity of proteins in interaction networks.

Tópicos

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Resumo

Genome-wide linkage and association studies have demonstrated promise in identifying genetic factors that influence health and disease. An important challenge is to narrow down the set of candidate genes that are implicated by these analyses. Protein-protein interaction (PPI) networks are useful in extracting the functional relationships between known disease and candidate genes, based on the principle that products of genes implicated in similar diseases are likely to exhibit significant connectivity/proximity. Information flow?based methods are shown to be very effective in prioritizing candidate disease genes. In this article, we utilize the topology of PPI networks to infer functional information in the context of disease association. Our approach is based on the assumption that PPI networks are organized into recurrent schemes that underlie the mechanisms of cooperation among different proteins. We hypothesize that proteins associated with similar diseases would exhibit similar topological characteristics in PPI networks. Utilizing the location of a protein in the network with respect to other proteins (i.e., the "topological profile" of the proteins), we develop a novel measure to assess the topological similarity of proteins in a PPI network. We then use this measure to prioritize candidate disease genes based on the topological similarity of their products and the products of known disease genes. We test the resulting algorithm, Vavien, via systematic experimental studies using an integrated human PPI network and the Online Mendelian Inheritance in Man (OMIM) database. Vavien outperforms other network-based prioritization algorithms as shown in the results and is available at www.diseasegenes.org.

Resumo Limpo

genomewid linkag associ studi demonstr promis identifi genet factor influenc health diseas import challeng narrow set candid gene implic analys proteinprotein interact ppi network use extract function relationship known diseas candid gene base principl product gene implic similar diseas like exhibit signific connectivityproxim inform flowbas method shown effect priorit candid diseas gene articl util topolog ppi network infer function inform context diseas associ approach base assumpt ppi network organ recurr scheme underli mechan cooper among differ protein hypothes protein associ similar diseas exhibit similar topolog characterist ppi network util locat protein network respect protein ie topolog profil protein develop novel measur assess topolog similar protein ppi network use measur priorit candid diseas gene base topolog similar product product known diseas gene test result algorithm vavien via systemat experiment studi use integr human ppi network onlin mendelian inherit man omim databas vavien outperform networkbas priorit algorithm shown result avail wwwdiseasegenesorg

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