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In many Gram-negative bacteria, the type III secretion system transports effector proteins into host cells, converting resources to bacterial advantage. Here we introduce a computational method that identifies type III effectors by combining homology-based inference with\n                    <jats:italic>de novo<\/jats:italic>\n                    predictions, reaching up to 3-fold higher performance than existing tools. Our work reveals that signals for recognition and transport of effectors are distributed over the entire protein sequence instead of being confined to the N-terminus, as was previously thought. Our scan of hundreds of prokaryotic genomes identified previously unknown effectors, suggesting that type III secretion may have evolved prior to the archaea\/bacteria split. Crucially, our method performs well for short sequence fragments, facilitating evaluation of microbial communities and rapid identification of bacterial pathogenicity \u2013 no genome assembly required. pEffect and its data sets are available at\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/services.bromberglab.org\/peffect\">http:\/\/services.bromberglab.org\/peffect<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/srep34516","type":"journal-article","created":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T05:37:35Z","timestamp":1475818655000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Computational prediction shines light on type III secretion origins"],"prefix":"10.1038","volume":"6","author":[{"given":"Tatyana","family":"Goldberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Rost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yana","family":"Bromberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,10,7]]},"reference":[{"key":"BFsrep34516_CR1","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1080\/09687860500042013","volume":"22","author":"IB Holland","year":"2005","unstructured":"Holland, I. 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