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However, currently available methods cannot identify which RNAi screen \"hits\" are novel components of well-characterized biological pathways known to regulate the interrogated phenotype. In this study, we describe a method to identify genes from RNAi datasets that are novel components of known biological pathways. We experimentally validate our approach in the context of a recently completed RNAi screen to identify novel regulators of melanogenesis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In this study, we utilize a PPI network topology-based approach to identify targets within our RNAi dataset that may be components of known melanogenesis regulatory pathways. Our computational approach identifies a set of screen targets that cluster topologically in a human PPI network with the known pigment regulator Endothelin receptor type B (EDNRB). Validation studies reveal that these genes impact pigment production and EDNRB signaling in pigmented melanoma cells (MNT-1) and normal melanocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We present an approach that identifies novel components of well-characterized biological pathways from functional genomics datasets that could not have been identified by existing statistical and computational approaches.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-4-84","type":"journal-article","created":{"date-parts":[[2010,6,16]],"date-time":"2010-06-16T06:13:59Z","timestamp":1276668839000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Protein interaction network topology uncovers melanogenesis regulatory network components within functional genomics datasets"],"prefix":"10.1186","volume":"4","author":[{"given":"Hsiang","family":"Ho","sequence":"first","affiliation":[]},{"given":"Tijana","family":"Milenkovi\u0107","sequence":"additional","affiliation":[]},{"given":"Vesna","family":"Memi\u0161evi\u0107","sequence":"additional","affiliation":[]},{"given":"Jayavani","family":"Aruri","sequence":"additional","affiliation":[]},{"given":"Nata\u0161a","family":"Pr\u017eulj","sequence":"additional","affiliation":[]},{"given":"Anand K","family":"Ganesan","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,6,15]]},"reference":[{"key":"473_CR1","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1093\/bfgp\/eln020","volume":"7","author":"B Lehner","year":"2008","unstructured":"Lehner B, Lee I: Network-guided genetic screening: building, testing and using gene networks to predict gene function. 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