Combining statistical alignment and phylogenetic footprinting to detect regulatory elements.
BACKGROUND
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.


BACKGROUND
SAPF is freely available to download online at http://www.stats.ox.ac.uk/~satija/SAPF/
Satija
Rahul
R
Department of Statistics, Oxford University, Oxford, UK. satija@stats.ox.ac.uk
Pachter
Lior
L
Hein
Jotun
J
D000465:Algorithms; D001483:Base Sequence; D018983:DNA Footprinting / Q000379:methods*; D003627:Data Interpretation, Statistical; D008969:Molecular Sequence Data; D010802:Phylogeny; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software