Combining statistical alignment and phylogenetic footprinting to detect regulatory elements

Rahul Satija, Lior Pachter, Jotun Hein

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1236-1242
Number of pages7
JournalBioinformatics
Volume24
Issue number10
DOIs
StatePublished - May 2008

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Phylogenetics
Uncertainty
Alignment
Transducers
Drosophila
Sequence Analysis
Genome
Prediction
Drosophilidae
Hidden Markov models
Transducer
Markov Model
Annotation
Datasets
Genes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Computational Theory and Mathematics
  • Computer Science Applications

Cite this

Combining statistical alignment and phylogenetic footprinting to detect regulatory elements. / Satija, Rahul; Pachter, Lior; Hein, Jotun.

In: Bioinformatics, Vol. 24, No. 10, 05.2008, p. 1236-1242.

Research output: Contribution to journalArticle

Satija, Rahul ; Pachter, Lior ; Hein, Jotun. / Combining statistical alignment and phylogenetic footprinting to detect regulatory elements. In: Bioinformatics. 2008 ; Vol. 24, No. 10. pp. 1236-1242.
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