Combining statistical alignment and phylogenetic footprinting to detect regulatory elements.

MOTIVATION: 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 fr...

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Main Authors: Satija, R, Pachter, L, Hein, J
Format: Journal article
Language:English
Published: 2008
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author Satija, R
Pachter, L
Hein, J
author_facet Satija, R
Pachter, L
Hein, J
author_sort Satija, R
collection OXFORD
description MOTIVATION: 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 hidden Markov model (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/
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spelling oxford-uuid:d0a94000-9aef-4cc3-85a8-56a30f7284842022-03-27T07:51:32ZCombining statistical alignment and phylogenetic footprinting to detect regulatory elements.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d0a94000-9aef-4cc3-85a8-56a30f728484EnglishSymplectic Elements at Oxford2008Satija, RPachter, LHein, J MOTIVATION: 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 hidden Markov model (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/
spellingShingle Satija, R
Pachter, L
Hein, J
Combining statistical alignment and phylogenetic footprinting to detect regulatory elements.
title Combining statistical alignment and phylogenetic footprinting to detect regulatory elements.
title_full Combining statistical alignment and phylogenetic footprinting to detect regulatory elements.
title_fullStr Combining statistical alignment and phylogenetic footprinting to detect regulatory elements.
title_full_unstemmed Combining statistical alignment and phylogenetic footprinting to detect regulatory elements.
title_short Combining statistical alignment and phylogenetic footprinting to detect regulatory elements.
title_sort combining statistical alignment and phylogenetic footprinting to detect regulatory elements
work_keys_str_mv AT satijar combiningstatisticalalignmentandphylogeneticfootprintingtodetectregulatoryelements
AT pachterl combiningstatisticalalignmentandphylogeneticfootprintingtodetectregulatoryelements
AT heinj combiningstatisticalalignmentandphylogeneticfootprintingtodetectregulatoryelements