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Several network-based frameworks have been developed to address this problem with varied results.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Result<\/jats:title>\n            <jats:p>We have developed a novel vertex similarity (VS) based parameter-free prioritizing framework to identify and rank orphan disease candidate genes. We validate our approach by using 1598 known orphan disease-causing genes (ODGs) representing 172 orphan diseases (ODs). We compare our approach with a state-of-art parameter-based approach (PageRank with Priors or PRP) and with another parameter-free method (Interconnectedness or ICN). Our results show that VS-based approach outperforms ICN and is comparable to PRP. We further apply VS-based ranking to identify and rank potential novel candidate genes for several ODs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>We demonstrate that VS-based parameter-free ranking approach can be successfully used for disease candidate gene prioritization and can complement other network-based methods for candidate disease gene ranking. Importantly, our VS-ranked top candidate genes for the ODs match the known literature, suggesting several novel causal relationships for further investigation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-6-s3-s8","type":"journal-article","created":{"date-parts":[[2012,12,17]],"date-time":"2012-12-17T13:14:54Z","timestamp":1355750094000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A vertex similarity-based framework to discover and rank orphan disease-related genes"],"prefix":"10.1186","volume":"6","author":[{"given":"Cheng","family":"Zhu","sequence":"first","affiliation":[]},{"given":"Akash","family":"Kushwaha","sequence":"additional","affiliation":[]},{"given":"Kenneth","family":"Berman","sequence":"additional","affiliation":[]},{"given":"Anil G","family":"Jegga","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2012,12,17]]},"reference":[{"issue":"3","key":"994_CR1","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1111\/j.1365-2125.2006.02654.x","volume":"62","author":"JWLP Dear","year":"2006","unstructured":"Dear JWLP, Webb DJ: Are rare diseases still orphans or happily adopted? 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