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Predicting functional upstream open reading frames in Saccharomyces cerevisiae

Selpi, Selpi, Bryant, CH, Kemp, GJL, Sarv, J, Kristiansson, E and Sunnerhagen, P 2009, 'Predicting functional upstream open reading frames in Saccharomyces cerevisiae' , BMC Bioinformatics, 10 , p. 451.

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Abstract

BACKGROUND: Some upstream open reading frames (uORFs) regulate gene expression (i.e., they are functional) and can play key roles in keeping organisms healthy. However, how uORFs are involved in gene regulation is not yet fully understood. In order to get a complete view of how uORFs are involved in gene regulation, it is expected that a large number of experimentally verified functional uORFs are needed. Unfortunately, wet-experiments to verify that uORFs are functional are expensive. RESULTS: In this paper, a new computational approach to predicting functional uORFs in the yeast Saccharomyces cerevisiae is presented. Our approach is based on inductive logic programming and makes use of a novel combination of knowledge about biological conservation, Gene Ontology annotations and genes' responses to different conditions. Our method results in a set of simple and informative hypotheses with an estimated sensitivity of 76%. The hypotheses predict 301 further genes to have 398 novel functional uORFs. Three (RPC11, TPK1, and FOL1) of these 301 genes have been hypothesised,following wet-experiments, by a related study to have functional uORFs. A comparison with another related study suggests that eleven of the predicted functional uORFs from genes LDB17, HEM3, CIN8, BCK2,PMC1, FAS1, APP1, ACC1, CKA2, SUR1, and ATH1 are strong candidates for wet-lab experimental studies. CONCLUSIONS: Learning based prediction of functional uORFs can be done with a high sensitivity. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help to elucidate the regulatory roles of uORFs.

Item Type: Article
Additional Information: BMC Bioinformatics is an Open Access journal.
Uncontrolled Keywords: machine learning, inductive logic programming, gene regulation
Themes: Subjects / Themes > Q Science > QA Mathematics > QA075 Electronic computers. Computer science
Subjects / Themes > Q Science > QH Natural history > QH301 Biology > QH426 Genetics
Subjects outside of the University Themes
Schools: Colleges and Schools > College of Science & Technology
Colleges and Schools > College of Science & Technology > School of Computing, Science and Engineering
Colleges and Schools > College of Science & Technology > School of Computing, Science and Engineering > Data Mining and Pattern Recognition Research Centre
Journal or Publication Title: BMC Bioinformatics
Publisher: BioMed Central Ltd, Floor 6, 236 Gray's Inn Road, London, WC1X 8HL, UK.
Refereed: Yes
ISSN: 1471-2105
Related URLs:
Depositing User: Dr Chris H. Bryant
Date Deposited: 11 Jan 2010 15:10
Last Modified: 20 Aug 2013 17:02
URI: http://usir.salford.ac.uk/id/eprint/2712

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