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We therefore took a comparative biology approach to predict protein-protein interactions across five species (human, mouse, fly, worm, and yeast) and developed InterologFinder for research biologists to easily navigate this data. We also developed a confidence score for interactions based on available experimental evidence and conservation across species.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The connectivity of the resultant networks was determined to have scale-free distribution, small-world properties, and increased local modularity, indicating that the added interactions do not disrupt our current understanding of protein network structures. We show examples of how these improved interactomes can be used to analyze a genome-scale dataset (RNAi screen) and to assign new function to proteins. Predicted interactions within this dataset were tested by co-immunoprecipitation, resulting in a high rate of validation, suggesting the high quality of networks produced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Protein-protein interactions were predicted in five species, based on orthology. An InteroScore, a score accounting for homology, number of orthologues with evidence of interactions, and number of unique observations of interactions, is given to each known and predicted interaction. Our website<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.interologfinder.org\" ext-link-type=\"uri\">http:\/\/www.interologfinder.org<\/jats:ext-link>provides research biologists intuitive access to this data.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1752-0509-4-36","type":"journal-article","created":{"date-parts":[[2010,4,23]],"date-time":"2010-04-23T18:15:52Z","timestamp":1272046552000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Building and analyzing protein interactome networks by cross-species comparisons"],"prefix":"10.1186","volume":"4","author":[{"given":"Amy M","family":"Wiles","sequence":"first","affiliation":[]},{"given":"Mark","family":"Doderer","sequence":"additional","affiliation":[]},{"given":"Jianhua","family":"Ruan","sequence":"additional","affiliation":[]},{"given":"Ting-Ting","family":"Gu","sequence":"additional","affiliation":[]},{"given":"Dashnamoorthy","family":"Ravi","sequence":"additional","affiliation":[]},{"given":"Barron","family":"Blackman","sequence":"additional","affiliation":[]},{"given":"Alexander JR","family":"Bishop","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,3,30]]},"reference":[{"key":"425_CR1","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/1471-2164-10-220","volume":"10","author":"L Wang","year":"2009","unstructured":"Wang L, Tu Z, Sun F: A network-based integrative approach to prioritize reliable hits from multiple genome-wide RNAi screens in Drosophila. 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