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Bioinformatics Advance Access originally published online on March 18, 2008
Bioinformatics 2008 24(10):1236-1242; doi:10.1093/bioinformatics/btn104
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Combining statistical alignment and phylogenetic footprinting to detect regulatory elements

Rahul Satija 1,*, Lior Pachter 2 and Jotun Hein 1

1Department of Statistics, Oxford University, Oxford, UK and 2Department of Mathematics, Univeristy of California, Berkeley, CA, USA

*To whom correspondence should be addressed.


  Abstract

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/

Contact: satija{at}stats.ox.ac.uk

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Limsoon Wong

Received on January 21, 2008; revised on February 21, 2008; accepted on March 17, 2008

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