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Nucleic Acids Research 2005 33(21):6743-6755; doi:10.1093/nar/gki977
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Published online 9 December 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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Article

Improved alignment of nucleosome DNA sequences using a mixture model

Ji-Ping Z. Wang* and Jonathan Widom1

Department of Statistics 2006 Sheridan Road, Evanston, IL 60208, USA 1Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University Evanston, IL 60208, USA

*To whom correspondence should be addressed. Tel: +1 847 467 6896; Fax: +1 847 491 4939; Email: jzwang{at}northwestern.edu

Received September 6, 2005. Revised October 22, 2005. Accepted November 7, 2005.

DNA sequences that are present in nucleosomes have a preferential ~10 bp periodicity of certain dinucleotide signals (1,2), but the overall sequence similarity of the nucleosomal DNA is weak, and traditional multiple sequence alignment tools fail to yield meaningful alignments. We develop a mixture model that characterizes the known dinucleotide periodicity probabilistically to improve the alignment of nucleosomal DNAs. We assume that a periodic dinucleotide signal of any type emits according to a probability distribution around a series of ‘hot spots’ that are equally spaced along nucleosomal DNA with 10 bp period, but with a 1 bp phase shift across the middle of the nucleosome. We model the three statistically most significant dinucleotide signals, AA/TT, GC and TA, simultaneously, while allowing phase shifts between the signals. The alignment is obtained by maximizing the likelihood of both Watson and Crick strands simultaneously. The resulting alignment of 177 chicken nucleosomal DNA sequences revealed that all 10 distinct dinucleotides are periodic, however, with only two distinct phases and varying intensity. By Fourier analysis, we show that our new alignment has enhanced periodicity and sequence identity compared with center alignment. The significance of the nucleosomal DNA sequence alignment is evaluated by comparing it with that obtained using the same model on non-nucleosomal sequences.

Correspondence may also be addressed to Jonathan Widom. Tel: +1 847 467 1887; Fax: +1 847 467 6489; Email: j-widom{at}northwestern.edu


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