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Combining Statistical Alignment and Phylogenetic Footprinting to Detect Regulatory Elements.Bioinformatics (18 March 2008)
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AbstractMOTIVATION: Traditional alignment-based phylogenetic footprinting approaches make predictions on the basis of a single assumed alignment. The predictions are therefore highly sensitive to alignment errors or regions of alignment uncertainty. Alternatively, statistical alignment methods provide a framework for performing phylogenetic analyses by examining a distribution of alignments. RESULTS: We developed a novel algorithm for predicting functional elements by combining statistical alignment and phylogenetic footprinting (SAPF). SAPF simultaneously performs both alignment and annotation by combining phylogenetic footprinting techniques with an HMM transducer-based multiple alignment model, and can analyze sequence data from multiple sequences. We assessed SAPF's predictive performance on two simulated datasets and three well-annotated cis-regulatory modules from newly sequenced Drosophila genomes. The results demonstrate that removing the traditional dependence on a single alignment can significantly augment the predictive performance, especially when there is uncertainty in the alignment of functional regions. AVAILABILITY: SAPF is freely available to download online at http://www.stats.ox.ac.uk/~satija/SAPF/ CONTACT: satija@stats.ox.ac.uk.
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