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There exist a number of <jats:italic>ab initio<\/jats:italic> gene prediction tools and they have been widely used for gene annotation for various species. However, existing tools are not optimized for identifying genes with highly variable GC content. In addition, some genes in grass genomes exhibit a sharp 5 <jats:sup>\u2032<\/jats:sup>- 3<jats:sup>\u2032<\/jats:sup> decreasing GC content gradient, which is not carefully modeled by available gene prediction tools. Thus, there is still room to improve the sensitivity and accuracy for predicting genes with GC gradients.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>In this work, we designed and implemented a new hidden Markov model (HMM)-based <jats:italic>ab initio<\/jats:italic> gene prediction tool, which is optimized for finding genes with highly variable GC contents, such as the genes with negative GC gradients in grass genomes. We tested the tool on three datasets from <jats:italic>Arabidopsis thaliana<\/jats:italic> and <jats:italic>Oryza sativa<\/jats:italic>. The results showed that our tool can identify genes missed by existing tools due to the highly variable GC contents.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>GPRED-GC can effectively predict genes with highly variable GC contents without manual intervention. It provides a useful complementary tool to existing ones such as Augustus for more sensitive gene discovery. The source code is freely available at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/sourceforge.net\/projects\/gpred-gc\/\">https:\/\/sourceforge.net\/projects\/gpred-gc\/<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12859-019-3047-3","type":"journal-article","created":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T09:02:35Z","timestamp":1577178155000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["GPRED-GC: a Gene PREDiction model accounting for 5 \u2032- 3\u2032 GC gradient"],"prefix":"10.1186","volume":"20","author":[{"given":"Prapaporn","family":"Techa-Angkoon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin L.","family":"Childs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1373-8023","authenticated-orcid":false,"given":"Yanni","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,24]]},"reference":[{"issue":"1","key":"3047_CR1","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1006\/jmbi.1997.0951","volume":"268","author":"C Burge","year":"1997","unstructured":"Burge C, Karlin S. 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